Meningoencephalitis with malacia caused by Sarcocystis calchasi in a rock pigeon in Japan.

Sarcocystis spp. cause pigeon protozoan encephalitis, a neuronal disease. A female pigeon exhibiting torticollis had a necrotic area in the cerebral hemisphere surrounded by lesions with perivascular cuffing, gliosis, granulomatous foci, and meningitis. Non-necrotic lesions were also observed in the brainstem. Intact and degenerative schizonts were observed within the neuropils and neurons in the lesions. Deoxyribonucleic acid (DNA) was extracted from paraffin-embedded brain tissues and genetically analyzed after gel electrophoresis to determine Sarcocystis spp. using specific primer sets for 28S ribosomal ribonucleic acid and internal transcribed spacer region-1. DNA sequencing confirmed a significant homology with S. calchasi. This is the first report of meningoencephalitis with malacia caused by S. calchasi in a rock pigeon in Japan.

Use of neurofilament light chain to identify structural brain diseases in dogs.

BACKGROUND: Neurofilament light chain (NfL) is released into the peripheral circulation by damaged axons. OBJECTIVES: To evaluate the diagnostic value of serum NfL concentration in dogs with intracranial diseases. ANIMALS: Study included 37 healthy dogs, 31 dogs with idiopathic epilepsy (IE), 45 dogs with meningoencephalitis of unknown etiology (MUE), 20 dogs with hydrocephalus, and 19 dogs with brain tumors. METHODS: Cohort study. Serum NfL concentrations were measured in all dogs using single-molecule array technology. RESULTS: Serum NfL concentration in dogs with each structural disease was significantly higher than in healthy dogs and dogs with IE (P = .01). The area under the receiver operating characteristic curve of NfL for differentiating between dogs with structural diseases and IE was 0.868. An optimal cutoff value of the NfL 27.10 pg/mL had a sensitivity of 86.67% and a specificity of 74.19% to differentiate the dogs with IE from those with structural brain diseases. There were significant correlations between NfL concentrations and lesion size: (1) MUE, P = .01, r = 0.429; (2) hydrocephalus, P = .01, r = 0.563. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum NfL could be a useful biomarker for distinguishing IE from structural diseases in dogs and predicting the lesion sizes of MUE and hydrocephalus.

Granulomatous meningoencephalitis and blindness associated with Mycobacterium tuberculosis complex infection in a senile female chimpanzee (Pan troglodytes).

A 40-year old female chimpanzee (Pan troglodytes) developed hyporexia, weight loss, followed by progressive and complete blindness. Tomography demonstrated an intracranial mass in the rostroventral brain involving the optic chiasm, with a presumptive diagnosis of neoplasm. However, histopathology revealed a granulomatous meningoencephalitis, and tissue samples tested positive for Mycobacterium tuberculosis.

Investigation of side effects to treatment and cause of death in 63 Scandinavian dogs suffering from meningoencephalitis of unknown origin: a retrospective study.

BACKGROUND: Meningoencephalitis of unknown origin is a common cause of severe neurological disease in dogs. The term covers a heterogeneous group of noninfectious inflammatory diseases, with immune dysregulation widely accepted as the underlying disease mechanism. Current treatment consists of immunosuppression, with corticosteroids being the mainstay of virtually all treatment regimens. However, side effects of corticosteroids can be severe, and might be the cause of death in some patients. This retrospective, multi-centric study aimed at describing a population of Scandinavian dogs with meningoencephalitis of unknown origin in regards to reported side effects and cause of death, and to highlight possible differences in survival, when comparing corticosteroid monotherapy with other treatment regimens. RESULTS: Within the 5-year study period, 63 dogs were included. Of these, 35 (49.3%) died or were euthanized during the study period. Median survival time from time of diagnosis based on Kaplan-Meier curves for the overall population was 714 days (equivalent to around 25 months, range 0-1678 days). There was no statistically significant difference (P = 0.31) in survival between dogs treated with corticosteroid monotherapy (n = 26, median survival time 716 days, equivalent to around 25 months, range 5-911 days), dogs receiving a combination of corticosteroids and ciclosporin (n = 15, median survival time 916 days, equivalent to around 31 months, range 35-1678 days), and dogs receiving corticosteroids combined with either cytosine arabinoside, leflunomide, or a combination of 2 or more add-on drugs (n = 13, median survival time 1186 days, equivalent to around 40 months, range 121-1640 days). Side effects were registered for 47/63 dogs. Polyphagia (n = 37/47), polyuria/polydipsia (n = 37/47), diarrhea (n = 29/47) and lethargy (n = 28/47) were most frequently reported. The most common cause for euthanasia was relapse (n = 15/35, 42.9%), followed by insufficient or lack of treatment response (n = 9, 25.7%). Side effects were the direct cause of euthanasia in 2/35 dogs (5.7%). CONCLUSIONS: A large proportion of dogs in the overall population were euthanized due to relapse, emphasizing a need for treatment regimens aimed at specifically preventing relapse for an improved long-term survival. Side effects in dogs receiving corticosteroid monotherapy were rarely a direct cause of death, but were reported for all dogs. No statistically significant difference in survival was found when corticosteroid monotherapy was compared to other treatment regimens.

Shared and unique antibody and B cell profiles in HIV-positive and HIV-negative individuals with cryptococcal meningoencephalitis.

Host non-T cell markers to aid in the diagnosis of cryptococcal meningoencephalitis (CM) have not been identified. In this case-control study, we characterized antibody and B cell profiles in HIV-negative and HIV-positive Vietnamese individuals of the Kinh ethnicity recently diagnosed with CM and controls. The study included 60 HIV-negative with no known immunocompromising condition and 60 HIV-positive individuals, with 30 CM cases and 30 controls in each group. Participants were matched by age, sex, HIV serostatus, and CD4 count in the HIV-positive group. Plasma immunoglobulin (Ig) levels, including IgG1, IgG2, IgM, and IgA, Cryptococcus spp. glucuronoxylomannan (GXM)- and laminarin (branched ${\rm{\beta }}$-[1-3]-glucan)-binding IgG, IgM, IgA levels, and peripheral blood B cell subsets were measured. Logistic regression, principal component, and mediation analyses were conducted to assess associations between antibody, B cell levels, and CM. The results showed that GXM-IgG levels were higher and IgG1 and IgG2 were lower in CM cases than controls, regardless of HIV status. In HIV-negative individuals, IgG2 mediated an inverse association between CD19+CD27+CD43+CD5- (B-1b-like) cells and CM. In HIV-positive individuals, lower levels of IgA, laminarin-IgA, and CD19+CD27+IgM+IgD- (IgM+ memory B) cells were each associated with CM. The shared and distinct antibody and B cell profiles identified in HIV-negative and HIV-positive CM cases may inform the identification of non-T-cell markers of CM risk or unsuspected disease, particularly in HIV-negative individuals.

Unlike cryptococcal meningitis (CM) in HIV-positive individuals, there are no known biomarkers of risk in HIV-negative individuals and the diagnosis is often not suspected and delayed. This study identified non-T cells, including antibody and B cell CM-associated profiles that may guide cryptococcal antigen testing in HIV-negative individuals.

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.

Assessment of oligoclonal bands in cerebrospinal fluid and serum of dogs with meningoencephalitis of unknown origin.

BACKGROUND: Meningoencephalitis of unknown origin (MUO) is an inflammatory disease of the canine central nervous system (CNS) that shares several features with multiple sclerosis (MS) in humans. In approximately 95% of MS patients, ≥ two immunoglobulin G (IgG) oligoclonal bands (OCBs) are detectable exclusively in the cerebrospinal fluid (CSF). HYPOTHESIS/OBJECTIVES: To investigate OCBs in CSF and serum in dogs affected by MUO, intervertebral disc disease (IVDD), idiopathic epilepsy (IE), intracranial neoplasia (IN), steroid-responsive meningitis-arteritis (SRMA), and diseases outside the CNS. We hypothesize that the highest prevalence of CSF-specific OCBs (≥ two OCBs uniquely in the CSF) would be found in dogs affected by MUO. ANIMALS: Client-owned dogs (n = 121) presented to the neurology service due to neurological deficits. METHODS: Prospective study. Measurement of IgG concentration in CSF and serum via a canine IgG ELISA kit. OCB detection via isoelectric focusing (IEF) and immunoblot. RESULTS: Presence of CSF-specific OCBs was significantly higher in dogs with MUO (57%) compared to 22% in IN, 6% in IE, 15% in SRMA, 13% in IVDD, and 0% in the non-CNS group (p < .001). Dogs with MUO were 9.9 times more likely to show CSF-specific OCBs than all other diseases together (95% confidence interval, 3.7-26.4; p < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: MUO showed the highest prevalence of CSF-specific OCBs, indicating an inflammatory B cell response. Future studies are needed to evaluate the prevalence in the specific MUO subtypes and a possible similarity with human MS.

Persistent marked cerebrospinal fluid eosinophilia in a dog with primary central nervous system histiocytic sarcoma.

A 6-year-old female spayed Jack Russell Terrier was evaluated for episodic seizure-like activity and intermittent obtundation over the previous 3 weeks. Magnetic resonance imaging (MRI) of the brain revealed mild generalized dilation of the ventricular system with periventricular edema. A focal area of mildly increased lepto- and pachymeningeal contrast uptake in the region of the right parietal and occipital lobes was observed. Analysis of cerebrospinal fluid (CSF) revealed marked mixed pleocytosis with 20% eosinophils and no atypical cells or microorganisms. The dog transiently improved with prednisolone for suspected eosinophilic meningoencephalitis/meningoencephalomyelitis of unknown origin (MUO) but worsened over the following 5 months. Brain MRI and CSF sampling were repeated. Additional multifocal lesions were evident in the brainstem and cerebellum. On CSF analysis, the eosinophilic pleocytosis and increased total protein persisted. The clinical signs progressed despite treatment, and the patient was euthanized 6 weeks later. A post-mortem examination was performed. Histopathology and immunohistochemistry revealed a multifocal neoplastic proliferation of cells in the brain, diffusely and strongly positive for ionized calcium-binding adapter molecule (Iba-1) and negative for AE1/AE3 pan-cytokeratin and glial-fibrillar-acid-protein (GFAP) immunostaining, consistent with a diagnosis of histiocytic sarcoma (HS). No other organic lesions were found; therefore, the neoplasm was considered a primary HS of the central nervous system (CNS). This case report stresses the importance of considering primary CNS HS in the differential diagnosis of dogs with marked CSF eosinophilia, even in the absence of atypical cells on cytologic examination.

Evaluation of the blood neutrophil-to-lymphocyte ratio as a biomarker for meningoencephalitis of unknown etiology in dogs.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been identified as a biomarker in several inflammatory and autoimmune diseases. Multiple sclerosis (MS) has been found to be associated with changes in the NLR in humans. OBJECTIVES: To examine the diagnostic value of the NLR in meningoencephalitis of unknown etiology (MUE) in dogs. ANIMALS: Thirty-eight MUE dogs, 20 hydrocephalic dogs, 10 brain tumor (BT) dogs, 32 idiopathic epilepsy (IE) dogs, and 41 healthy dogs. METHODS: Retrospective study. Medical records were reviewed to identify dogs with a diagnosis of neurologic disease. The NLR was determined in all dogs. RESULTS: The median NLR was significantly higher in MUE dogs (6.08) than in healthy (1.78, P < .001), IE (2.50, P < .05), and hydrocephalic dogs (1.79, P < .05). The area under the receiver operating characteristic curve of the NLR for differentiation between MUE and healthy dogs was 0.96, and between the MUE dogs and dogs with other forebrain diseases was 0.86. An optimal cutoff of 4.16 for the NLR had a sensitivity of 71.1% and specificity of 83.9% to differentiate the MUE dogs from the dogs with other forebrain diseases. CONCLUSIONS AND CLINICAL IMPORTANCE: The NLR could be a biomarker for diagnosing MUE and distinguishing it from other intracranial diseases in dogs.

Neuroinflammatory diseases of the central nervous system of dogs: A retrospective study of 207 cases (2008-2019).

In this study we describe 207 cases of neuroinflammatory diseases of the central nervous system (CNS) in dogs autopsied at the Athens Veterinary Diagnostic Laboratory (University of Georgia, United States) from 2008 to 2019. Idiopathic and infectious diseases were diagnosed in 111 cases (53.6%) and 96 cases (46.4%), respectively. Idiopathic diseases consisted of granulomatous meningoencephalomyelitis (n = 42; 37.8% of idiopathic cases), nonspecific lymphoplasmacytic meningoencephalomyelitis (n = 39; 35.1%), necrotizing meningoencephalomyelitis (n = 22; 19.8%), presumed steroid-responsive meningitis-arteritis (n = 6; 5.4%), and necrotizing leukoencephalitis (n = 2; 1.8%). Infectious diseases consisted of bacterial infections (n = 49; 51% of infectious cases), viral infections (n = 39; 40.6%), fungal infections (n = 5; 5.2%), and parasitic infections (n = 3; 3.1%). Our study provides an overview of the most frequent neuroinflammatory diseases of the CNS of dogs in our diagnostic routine; indicates that a comprehensive diagnostic approach, including a thorough evaluation of the pathology findings and ancillary laboratory testing results, is important for an adequate diagnosis of neurologic diseases in dogs; and underscores the problems associated with the variability in tissue sample collection methods among cases. The great number of nonspecific lymphoplasmacytic meningoencephalitis also highlights the need for development of molecular laboratory tests to identify potential infectious agents in these cases.

Maladies neuro-inflammatoires du système nerveux central du chien : étude rétrospective de 207 cas (2008­2019). Dans cette étude, nous décrivons 207 cas de maladies neuro-inflammatoires du système nerveux central (SNC) chez des chiens autopsiés au Athens Veterinary Diagnostic Laboratory (University of Georgia, États-Unis) de 2008 à 2019. Des maladies idiopathiques et infectieuses ont été diagnostiquées dans 111 cas (53,6 %) et 96 cas (46,4 %), respectivement. Les maladies idiopathiques consistaient en : méningo-encéphalomyélite granulomateuse (n = 42; 37,8 % des cas idiopathiques), méningo-encéphalomyélite lymphoplasmocytaire non spécifique (n = 39; 35,1 %), méningo-encéphalomyélite nécrosante (n = 22; 19,8 %), méningite-artérite corticosensible présumée (n = 6; 5,4 %) et leucoencéphalite nécrosante (n = 2; 1,8 %). Les maladies infectieuses comprenaient des infections bactériennes (n = 49; 51 % des cas infectieux), des infections virales (n = 39; 40,6 %), des infections fongiques (n = 5; 5,2 %), et des infections parasitaires (n = 3; 3,1 %). Notre étude donne un aperçu des maladies neuro-inflammatoires du SNC des chiens les plus fréquentes dans notre routine de diagnostic; indique qu'une approche diagnostique complète, comprenant une évaluation approfondie des résultats de la pathologie et des résultats des tests de laboratoire auxiliaires, est importante pour un diagnostic adéquat des maladies neurologiques chez les chiens; et souligne les problèmes associés à la variabilité des méthodes de prélèvement d'échantillons de tissus entre les cas. Le grand nombre de méningo-encéphalites lymphoplasmocytaires non spécifiques souligne également la nécessité de développer des tests de laboratoire moléculaire pour identifier les agents infectieux potentiels dans ces cas.(Traduit par Dr Serge Messier).

Production of granulomas in Mycoplasma bovis infection associated with meningitis-meningoencephalitis, endocarditis, and pneumonia in cattle.

Mycoplasma bovis, the most important primary pathogen in the family Mycoplasmataceae, causes pneumonia, arthritis, otitis media, and mastitis in cattle. Histopathologic pulmonary changes associated with M. bovis infection have been characterized as suppurative-to-caseonecrotic bronchopneumonia; infection in other organs has been reported in only a few studies that examined caseonecrotic endocarditis and suppurative meningitis. Granulomatous lesions associated with M. bovis infection have been reported only rarely. We studied the granulomatous inflammation associated with M. bovis infection in several organs of 21 Japanese Black cattle. M. bovis was detected by isolation and loop-mediated isothermal amplification methods; other bacteria were detected using culture on 5% blood sheep agar and a MALDI-TOF MS Biotyper. Tissues were examined by histopathology and by immunohistochemistry (IHC) using anti-M. bovis, anti-Iba1, anti-iNOS, and anti-CD204 antibodies. All 21 cases, which included 2 cases of meningitis-meningoencephalitis, 8 cases of endocarditis, and 11 cases of bronchopneumonia, had caseonecrotic granulomatous inflammation associated with M. bovis infection. The IHC for macrophages revealed a predominance of iNOS-labeled (M1) macrophages in the inner layer of the caseonecrotic granulomas associated with meningitis-meningoencephalitis, endocarditis, and bronchopneumonia in Japanese Black cattle naturally infected with M. bovis.

Leptospiral meningoencephalitis in a raccoon dog.

Neuroleptospirosis is a rare disease caused by pathogenic Leptospira interrogans in humans; however, it has not been fully studied in animals. A young wild raccoon dog was found convulsing in the recumbent position and died the next day. Histologic examination revealed nonsuppurative meningoencephalitis in the cerebrum, cerebellum, midbrain, and medulla oblongata. The lesions consisted of mixed infiltrates of Iba1-positive macrophages and CD3-positive T cells, with a small number of CD79α-positive B cells and myeloperoxidase-positive neutrophils. In the frontal cortex, perivascular cuffs and adjacent microglial nodules were distributed diffusely, especially in the molecular layer. Glial nodules were comprised of Iba1- and myeloperoxidase-positive activated microglia. Immunohistochemistry revealed leptospires in mononuclear cell perivascular cuffs, but not in glial nodules. Neuroleptospirosis was accompanied by Leptospira-related nonsuppurative interstitial nephritis, pulmonary edema and hemorrhage, and coronary periarteritis, as well as Toxocara tanuki in the small intestine and nonspecific foreign-body granulomas in the lungs and stomach.

Meningoencephalitis caused by Bovine alphaherpesvirus 5 in Pernambuco, Brazil / [Meningoencefalite causada pelo Bovine alphaherpesvirus 5 em Pernambuco, Brasil]

Objetivou-se descrever a ocorrência do Bovine alphaherpesvirus 5 (BoHV5) como causa de meningoencefalite não supurativa em bovinos do estado de Pernambuco, Brasil. Para tanto, 32 amostras de sistema nervoso embebidas em parafina foram obtidas de animais acometidos por doenças neurológicas atendidos na Clínica de Bovinos de Garanhuns da Universidade Federal Rural de Pernambuco (CBG-UFRPE), entre 2012 e 2016. As amostras foram analisadas quanto à presença do gene da glicoproteína C do BoHV5 por reação em cadeia da polimerase (PCR). Dois animais (6,25%) tiveram resultado positivo à PCR, e sua análise de sequenciamento indicou 100% de similaridade para o BoHV5. Os resultados histopatológicos desses dois animais revelaram lesões multifocais de meningoencefalite não supurativa associada à polioencefalomalácia, presença de corpúsculos de inclusão basofílicos, infiltração de células de Gitter e presença de manguitos perivasculares. A PCR se mostra uma importante ferramenta para diferenciação das infecções por BoHV5 de outras enfermidades neurológicas de bovinos, especialmente a raiva.(AU)

Biomarkers of non-infectious inflammatory CNS diseases in dogs - Where are we now? Part I: Meningoencephalitis of unknown origin.

Meningoencephalitides of Unknown Origin (MUO) comprises a group of non-infectious inflammatory brain conditions, which frequently cause severe neurological disease and death in dogs. Although multiple diagnostic markers have been investigated, a conclusive diagnosis, at present, essentially relies on postmortem histopathology. However, different groups of biomarkers, e.g. acute phase proteins, antibodies, cytokines, and neuro-imaging markers may prove useful in the diagnostic investigation of dogs with MUO. It appears from the current literature that acute phase proteins such as C-reactive protein are often normal in MUO, but may be useful to rule out steroid responsive meningitis-arteritis as well as other systemic inflammatory conditions. In antibody research, anti-glial fibrillary acidic protein (GFAP) may play a role, but further research is needed to establish this as a consistent marker of particularly Pug dog encephalitis. The proposed diagnostic markers often lack specificity to distinguish between the subtypes of MUO, but an increased expression of interferon-γ (IFN-γ) in necrotizing meningoencephalitis (NME) and interleukin-17 (IL-17) in granulomatous meningoencephalitis (GME) in tissue biopsies may indicate their potential as specific markers of NME and GME, respectively, suggesting further investigations of these in serum and CSF. While neuro-imaging is already an important part of the diagnostic work-up in MUO, further promising results have been shown with Positron Emission Tomography (PET) as well as proton resonance spectroscopy (1H MRS), which may be able to detect areas of necrosis and granulomas, respectively, with relatively high specificity. This review presents different groups of established and potential diagnostic markers of MUO assessing current results and future potential.

Cerebrospinal fluid analysis lacks diagnostic specificity in dogs with vestibular disease.

BACKGROUND: Although, vestibular syndrome is a common neurological presentation, little is known about the diagnostic value of cerebrospinal fluid (CSF) analysis in vestibular syndrome in dogs. METHODS: Medical records were retrospectively reviewed, and dogs with vestibular disease that had undergone magnetic resonance imaging of the head, CSF analysis and were diagnosed with central or peripheral vestibular syndrome were included. Disorders affecting the central vestibular system included meningoencephalitis of unknown origin (MUO), brain neoplasia, ischaemic infarct, intracranial empyema or metronidazole toxicity. Disorders affecting the peripheral vestibular system included idiopathic vestibular disease, otitis media/interna or neoplasia affecting the inner ear structures. Total nucleated cell concentration (TNCC), total protein concentration (TP) and cytologic assessment were recorded. RESULTS: A total of 102 dogs met the inclusion criteria. The sensitivity and specificity of increased CSF TNCC to differentiate central from peripheral vestibular syndrome was 49% and 90%, while the sensitivity and specificity of increased TP was 58% and 39%, respectively. The TNCC and TP in dogs with MUO were significantly higher than in dogs with idiopathic vestibular disease (p = 0.000 and p = 0.004). MUO was associated with lymphocytic pleocytosis, while idiopathic vestibular disease and ischaemic infarct were associated with the presence of activated macrophages or normal cytology (p = 0.000). CONCLUSION: Although consistent CSF abnormalities were observed in dogs with MUO, CSF analysis did not allow reliable differentiation between central and peripheral vestibular syndrome. CSF analysis is not reliable as the sole diagnostic technique in dogs with vestibular disease.

Fatal Meningoencephalitis From a Rhizomucor pusillus Infection in a Juvenile Magellanic Penguin (Spheniscus magellanicus).

A 7-month-old, male Magellanic penguin (Spheniscus magellanicus), housed in an outdoor exhibit, developed acute neurologic signs that progressed to death over 2 days. On gross examination, the bird had congested, edematous lungs, and cerebellar hemorrhage. Histologic examination identified granulomatous pneumonia and encephalitis, with thrombosis and eosinophilic, branching fungal hyphae that had invaded the meningeal vessel walls. Polymerase chain reaction identified the fungus in the brain as Rhizomucor pusillus, an uncommon cause of mucormycosis. This organism has previously been reported in respiratory, skeletal, and sino-orbital lesions of avian species. This clinical report describes meningoencephalitis associated with Rhizomucor pusillus in a penguin.

Recombinant bovine IL17A acts as an adjuvant for bovine herpesvirus vaccine.

The Bovine herpes virus type 5 glycoprotein D (gD) is essential for viral penetration into host permissive cells. The Herpes virus gD glycoprotein has been used for bovine immunization, being efficient in reduction of viral replication, shedding and clinical signs, however sterilizing immunity is still not achieved. Recombinant subunit vaccines are, in general, poorly immunogenic requiring additional adjuvant components. Interleukin 17A (IL17A) is a pro-inflammatory cytokine produced by T helper 17 cells that mediate mucosal immunity. IL17 production during vaccine-induced immunity is a requirement for mucosal protection to several agents. In this study, we investigated the potential of a recombinant IL17A to act as an adjuvant for a recombinant BoHV-5 glycoprotein D vaccine in cattle. Three cattle groups were divided as: group 1) rgD5 + alumen + rIL-17A; 2) rgD5 + alumen; and 3) PBS + alumen. The cattle (3 per group) received two doses of their respective vaccines at an interval of 21 days. The group that received rIL17 in its vaccine formulation at the 7th day after the prime immunization had significant higher levels of specific rgD-IgG than the alumen group. Addition of rIL17 also led to a significant fold increase in specific anti-rgD IgG and neutralizing antibodies to the virus, respectively, when compared with the alumen group. Cells stimulated with rIL17A responded with IL17 transcription, as well IL2, IL4, IL10, IL15, Bcl6 and CXCR5. Our findings suggest that the rIL17A has adjuvant potential for use in vaccines against BoHV-5 as well as potentially other pathogens of cattle.

[Diagnostics in epilepsy - potential of magnetic resonance imaging]. / Diagnostik der Epilepsie ­ Möglichkeiten der Magnetresonanztomografie.

Epilepsy is a common neurologic disease frequently encountered by small animal practitioners. The disease comprises a multiplicity of clinical presentations and etiologies and often necessitates a comprehensive as well as cost-intensive diagnostic workup. This is mandatory in order to be able to diagnose or exclude a metabolic cause of the seizures and to distinguish between idiopathic and structural epilepsy. The examination by means of magnetic resonance imaging (MRI) represents a central component of the diagnostic workup, which in turn has essential effects on treatment and prognosis. In order to achieve standardized examination and comparable results, it is of utmost importance to use defined MRI protocols. Accordingly, communication and interaction between clinical institutions may be facilitated and as of yet undetected structural changes might be recorded in future MRI techniques. This review article sets particularly emphasis on the definition and classification of epilepsy as well as its diagnostic imaging procedures and refers to statistics and specialists' recommendations for the diagnostic workup in dogs.

Classification of neoplastic and inflammatory brain disease using MRI texture analysis in 119 dogs.

Magnetic resonance imaging is the primary method used to diagnose canine glial cell neoplasia and noninfectious inflammatory meningoencephalitis. Subjective differentiation of these diseases can be difficult due to overlapping imaging characteristics. This study utilizes texture analysis (TA) of intra-axial lesions both as a means to quantitatively differentiate these broad categories of disease and to help identify glial tumor grade/cell type and specific meningoencephalitis subtype in a group of 119 dogs with histologically confirmed diagnoses. Fifty-nine dogs with gliomas and 60 dogs with noninfectious inflammatory meningoencephalitis were retrospectively recruited and randomly split into training (n = 80) and test (n = 39) cohorts. Forty-five of 120 texture metrics differed significantly between cohorts after correcting for multiple testing (false discovery rate < 0.05). After training the random forest algorithm, the classification accuracy for the test set was 85% (sensitivity 89%, specificity 81%). TA was only partially able to differentiate the inflammatory subtypes (granulomatous meningoencephalitis [GME], necrotizing meningoencephalitis [NME], and necrotizing leukoencephalitis [NLE]) (out-of-bag error rate of 35.0%) and was unable to identify metrics that could correctly classify glioma grade or cell type (out-of-bag error rate of 59.6% and 47.5%, respectively). Multiple demographic differences, such as patient age, sex, weight, and breed were identified between disease cohorts and subtypes which may be useful in prioritizing differential diagnoses. TA of MR images with a random forest algorithm provided classification accuracy of inflammatory and neoplastic brain disease approaching the accuracy of previously reported subjective radiologist evaluation.

Diagnostic evaluation of fatal Balamuthia mandrillaris meningoencephalitis in a captive Bornean orangutan (Pongo pygmaeus) with identification of potential environmental source and evidence of chronic exposure.

A female Bornean orangutan (Pongo pygmaeus) aged 11 years and 6 months was examined by veterinarians after caretakers observed lethargy and facial grimacing. Within 72 h the primate had left-sided hemiparesis that worsened over the next week. An MRI revealed a focal right-sided cerebral mass suspected to be a neoplasm. Ten days after onset of clinical signs, the orangutan died. On postmortem exam, the medial right parietal lobe was replaced by a 7 × 4 × 3.5 cm focus of neuromalacia and hemorrhage that displaced the lateral ventricle and abutted the corpus callosum. Histopathology of the cerebral lesion revealed pyogranulomatous meningoencephalitis with intralesional amoeba trophozoites and rare cysts. Fresh parietal lobe was submitted to the Centers for Disease Control and Prevention lab for multiplex free-living amoebae real-time PCR and detected Balamuthia mandrillaris DNA at a high burden. Mitochondrial DNA was sequenced, and a 760-bp locus 19443F/20251R was compared to several human infections of B. mandrillaris and shown to be identical to the isolates from four human cases of encephalitis: 1998 in Australia, 1999 in California, 2000 in New York, and 2010 in Arizona. Indirect immunofluorescent antibody testing of stored serum samples indicated exposure to B. mandrillaris for at least 2 years prior to death. Within 1 week of the orangutan's death, water from the exhibit was analyzed and identified the presence of B. mandrillaris DNA, elucidating a possible source of exposure. B. mandrillaris, first reported in a mandrill in 1986, has since occurred in humans and animals and is now considered an important emerging pathogen.