PCYT2 deficiency in Saarlooswolfdogs with progressive retinal, central, and peripheral neurodegeneration.

We investigated a syndromic disease comprising blindness and neurodegeneration in 11 Saarlooswolfdogs. Clinical signs involved early adult onset retinal degeneration and adult-onset neurological deficits including gait abnormalities, hind limb weakness, tremors, ataxia, cognitive decline and behavioral changes such as aggression towards the owner. Histopathology in one affected dog demonstrated cataract, retinal degeneration, central and peripheral axonal degeneration, and severe astroglial hypertrophy and hyperplasia in the central nervous system. Pedigrees indicated autosomal recessive inheritance. We mapped the suspected genetic defect to a 15 Mb critical interval by combined linkage and autozygosity analysis. Whole genome sequencing revealed a private homozygous missense variant, PCYT2:c.4A>G, predicted to change the second amino acid of the encoded ethanolamine-phosphate cytidylyltransferase 2, XP_038402224.1:(p.Ile2Val). Genotyping of additional Saarlooswolfdogs confirmed the homozygous genotype in all eleven affected dogs and demonstrated an allele frequency of 9.9% in the population. This experiment also identified three additional homozygous mutant young dogs without overt clinical signs. Subsequent examination of one of these dogs revealed early-stage progressive retinal atrophy (PRA) and expansion of subarachnoid CSF spaces in MRI. Dogs homozygous for the pathogenic variant showed ether lipid accumulation, confirming a functional PCYT2 deficiency. The clinical and metabolic phenotype in affected dogs shows some parallels with human patients, in whom PCYT2 variants lead to a rare form of spastic paraplegia or axonal motor and sensory polyneuropathy. Our results demonstrate that PCYT2:c.4A>G in dogs cause PCYT2 deficiency. This canine model with histopathologically documented retinal, central, and peripheral neurodegeneration further deepens the knowledge of PCYT2 deficiency.

LISTERIA MONOCYTOGENES INFECTION IN FREE-RANGING RED FOXES (VULPES VULPES) AND EURASIAN LYNX (LYNX LYNX) IN SWITZERLAND.

Listeria monocytogenes is an ubiquitous environmental saprophytic bacterium causing listeriosis in domestic animals, humans, and occasionally wildlife. In animals, this foodborne zoonotic disease mainly occurs in ruminants and it is rare in carnivores. Seven red foxes (Vulpes vulpes) and one Eurasian lynx (Lynx lynx) were diagnosed with listeriosis between 2010 and 2021 at the Institute for Fish and Wildlife Health, Bern, Switzerland. Necropsy and histopathology revealed meningitis (six of seven red foxes), hepatitis (six of seven red foxes), pneumonia (five of seven red foxes), splenitis (two of seven red foxes) and splenomegaly (the Eurasian lynx, two of seven red foxes). Listeria monocytogenes was isolated from either lung, spleen, liver, or kidney of all animals. Serotyping detected L. monocytogenes serotype 1/2a in five red foxes and the Eurasian lynx and serotype 4b in two red foxes. Six red foxes were positive for canine distemper virus (CDV) by polymerase chain reaction, whereas the Eurasian lynx and one red fox were negative. One red fox that was positive for CDV and listeriosis was also diagnosed with salmonellosis. The identified L. monocytogenes serotypes are among the three most frequently isolated serotypes (1/2a, 1/2b, and 4b) from food or the food production environment and those that cause most listeriosis cases in humans and animals. Coinfection with CDV in six red foxes questions the role of CDV as potential predisposing factor for septicemic listeriosis. The detection of listeriosis in the regionally endangered Eurasian lynx and in carnivores highly abundant in urban settings, such as red foxes, reinforces the importance of wildlife health surveillance in a One Health context and adds the Eurasian lynx to the list of carnivores susceptible to the disease. Further investigations are required to assess the prevalence and epidemiology of L. monocytogenes in free-ranging carnivores and its interaction with CDV.

DYRK1B haploinsufficiency in a Holstein cattle with epilepsy.

In this study, epilepsy with focal seizures progressing to generalized seizures was diagnosed in a 6-month-old Holstein heifer. The seizures were characterized by a brief pre-ictal phase with depression and vocalization. During the ictal phase eyelid spasms, tongue contractions, nodding and abundant salivation were observed, rapidly followed by a convulsive phase with bilateral tonic, clonic or tonic-clonic activity and loss of consciousness. Finally, during the postictal phase the heifer was obtunded and disorientated, unable to perceive obstacles and hypermetric, and pressed its head against objects. In the inter-seizure phase, the heifer was clinically normal. Neuropathology revealed axonal degeneration in the brainstem and diffuse astrocytic hypertrophic gliosis. Whole genome sequencing of the affected heifer identified a private heterozygous splice-site variant in DYRK1B (NM_001081515.1: c.-101-1G>A), most likely resulting in haploinsufficiency owing to loss-of-function. This represents a report of a DYRK1B-associated disease in cattle and adds DYRK1B to the candidate genes for epilepsy.

Machine learning predicts histologic type and grade of canine gliomas based on MRI texture analysis.

Conventional MRI features of canine gliomas subtypes and grades significantly overlap. Texture analysis (TA) quantifies image texture based on spatial arrangement of pixel intensities. Machine learning (ML) models based on MRI-TA demonstrate high accuracy in predicting brain tumor types and grades in human medicine. The aim of this retrospective, diagnostic accuracy study was to investigate the accuracy of ML-based MRI-TA in predicting canine gliomas histologic types and grades. Dogs with histopathological diagnosis of intracranial glioma and available brain MRI were included. Tumors were manually segmented across their entire volume in enhancing part, non-enhancing part, and peri-tumoral vasogenic edema in T2-weighted (T2w), T1-weighted (T1w), FLAIR, and T1w postcontrast sequences. Texture features were extracted and fed into three ML classifiers. Classifiers' performance was assessed using a leave-one-out cross-validation approach. Multiclass and binary models were built to predict histologic types (oligodendroglioma vs. astrocytoma vs. oligoastrocytoma) and grades (high vs. low), respectively. Thirty-eight dogs with a total of 40 masses were included. Machine learning classifiers had an average accuracy of 77% for discriminating tumor types and of 75.6% for predicting high-grade gliomas. The support vector machine classifier had an accuracy of up to 94% for predicting tumor types and up to 87% for predicting high-grade gliomas. The most discriminative texture features of tumor types and grades appeared related to the peri-tumoral edema in T1w images and to the non-enhancing part of the tumor in T2w images, respectively. In conclusion, ML-based MRI-TA has the potential to discriminate intracranial canine gliomas types and grades.

MRI ischemic and hemorrhagic lesions in arterial and venous territories characterize central nervous system intravascular lymphoma in dogs.

Intravascular lymphoma (IVL) is characterized by the proliferation of large malignant lymphocytes within the lumen of blood vessels. This retrospective, multi-center, case series study aimed to describe the MRI features of confirmed central nervous system IVL in dogs and compare them with histopathological findings. Medical record databases from seven veterinary centers were searched for cases of histologically confirmed IVL. Dogs were included if an MRI was performed. The MRI studies and histopathology samples were reviewed to compare the MRI changes with the histopathological findings. Twelve dogs met the inclusion criteria (12 brains and three spinal cords). Imaging of the brains revealed multifocal T2-weighted/FLAIR hyperintense and T1-weighted iso-hypointense lesions, with variable contrast enhancement; areas of abnormal diffusion both in arterial and venous territories in diffusion-weighted imaging; and meningeal enhancement. On gradient echo images (GRE), the changes comprised tubular susceptibility artifacts, consistent with the "susceptibility vessel sign", and additional variably sized/shaped intraparenchymal susceptibility artifacts. Spinal cord lesions presented as fusiform T2-weighted hyperintensities with scattered susceptibility artifacts on GRE and variable parenchymal and meningeal contrast enhancement. On histopathology, subarachnoid hemorrhages and neuroparenchymal areas of edema and necrosis, with or without hemorrhage, indicating ischemic and hemorrhagic infarctions, were found. These lesions were concurrent with severely dilated meningeal and parenchymal arteries and veins plugged by neoplastic lymphocytes and fibrin. Due to the unique angiocentric distribution of IVL, ischemic and hemorrhagic infarcts of variable chronicity affecting both the arterial and venous territories associated with thrombi formation can be detected on MRI.

Bovine neutrophil chemotaxis to Listeria monocytogenes in neurolisteriosis depends on microglia-released rather than bacterial factors.

BACKGROUND: Listeria monocytogenes (Lm) is a bacterial pathogen of major concern for humans and ruminants due to its neuroinvasive potential and its ability to cause deadly encephalitis (neurolisteriosis). On one hand, polymorphonuclear neutrophils (PMN) are key players in the defense against Lm, but on the other hand intracerebral infiltration with PMN is associated with significant neural tissue damage. Lm-PMN interactions in neurolisteriosis are poorly investigated, and factors inducing PMN chemotaxis to infectious foci containing Lm in the central nervous system (CNS) remain unidentified. METHODS: In this study, we assessed bovine PMN chemotaxis towards Lm and supernatants of infected endogenous brain cell populations in ex vivo chemotaxis assays, to identify chemotactic stimuli for PMN chemotaxis towards Lm in the brain. In addition, microglial secretion of IL-8 was assessed both ex vivo and in situ. RESULTS: Our data show that neither Lm cell wall components nor intact bacteria elicit chemotaxis of bovine PMN ex vivo. Moreover, astrocytes and neural cells fail to induce bovine PMN chemotaxis upon infection. In contrast, supernatant from Lm infected microglia readily induced chemotaxis of bovine PMN. Microglial expression and secretion of IL-8 was identified during early Lm infection in vitro and in situ, although IL-8 blocking with a specific antibody could not abrogate PMN chemotaxis towards Lm infected microglial supernatant. CONCLUSIONS: These data provide evidence that host-derived rather than bacterial factors trigger PMN chemotaxis to bacterial foci in the CNS, that microglia have a primary role as initiators of bovine PMN chemotaxis into the brain during neurolisteriosis and that blockade of these factors could be a therapeutic target to limit intrathecal PMN chemotaxis and PMN associated damage in neurolisteriosis.

Listeria monocytogenes at the interface between ruminants and humans: A comparative pathology and pathogenesis review.

The bacterium Listeria monocytogenes (Lm) is widely distributed in the environment as a saprophyte, but may turn into a lethal intracellular pathogen upon ingestion. Invasive infections occur in numerous species worldwide, but most commonly in humans and farmed ruminants, and manifest as distinct forms. Of those, neuroinfection is remarkably threatening due to its high mortality. Lm is widely studied not only as a pathogen but also as an essential model for intracellular infections and host-pathogen interactions. Many aspects of its ecology and pathogenesis, however, remain unclear and are rarely addressed in its natural hosts. This review highlights the heterogeneity and adaptability of Lm by summarizing its association with the environment, farm animals, and disease. It also provides current knowledge on key features of the pathology and (molecular) pathogenesis of various listeriosis forms in naturally susceptible species with a special focus on ruminants and on the neuroinvasive form of the disease. Moreover, knowledge gaps on pathomechanisms of listerial infections and relevant unexplored topics in Lm pathogenesis research are highlighted.

MRI features of canine hemangiosarcoma affecting the central nervous system.

Hemangiosarcoma is the most common metastatic tumor involving the brain in dogs but detailed published descriptions of the magnetic resonance imaging (MRI) features are lacking. The objective of this multi-center, retrospective case series study was to describe MRI characteristics of canine hemangiosarcoma affecting the central nervous system (CNS). Medical records of seven referral institutions were retrospectively reviewed. Dogs were included if they had a histopathologically confirmed diagnosis of hemangiosarcoma affecting the CNS and undergone an MRI of the brain and/or vertebral column. Lesions were independently evaluated by two observers. Twenty dogs met the inclusion criteria and one dog had both intracranial and intramedullary hemangiosarcoma. Consistent MRI features included heterogeneous (17/21) lesions in all sequences with mainly mixed signal intensity (12/21), presence of susceptibility artifact on T2*w (15/16), associated moderate to severe perilesional edema (21/21), and moderate to strong (20/21) heterogeneous (14/21) or ring-like (6/21) contrast enhancement. Intracranial hemangiosarcoma was frequently multiple and intra-axial, affecting consistently the telencephalon and no differences in MRI features were found between primary and metastatic hemangiosarcoma. This is the first MRI description of primary intracranial hemangiosarcoma and primary intracranial epithelioid hemangiosarcoma. Vertebral hemangiosarcomas were segmental poorly marginated polyostotic and highly aggressive lesions invading the thoracic vertebral canal and paraspinal tissues. Epidural hemangiosarcomas were single and well-marginated lesions in the thoracolumbar and/or lumbar region. Intramedullary hemangiosarcomas were cervical, metastatic in origin, and frequently (3/4) accompanied by intracranial lesions. These described MRI features will aid early identification of hemangiosarcoma guiding subsequent diagnostics and therapeutics.

Can MRI differentiate between ring-enhancing gliomas and intra-axial abscesses?

Gliomas of the brain may appear as expansile ring-enhancing masses in MRI studies, mimicking the appearance of intra-axial abscesses. The aims of this study were to compare the MRI features of ring-enhancing gliomas and intra-axial brain abscesses in dogs and cats and to identify the characteristics that might help differentiate them. For this multicenter, retrospective, and observational study, the inclusion criteria were as follows: (a) a definitive diagnosis of glioma or abscess based on cytological or histopathological examination following CSF collection or surgical biopsy/necropsy, respectively; (b) MRI study performed with a high- or low-field MRI scanner, including a same plane T1W pre- and postcontrast, a T2W and a T2 FLAIR sequence in at least one plane. If available, delayed T1W postcontrast, T2*W GE, DWI/ADC, and SWI sequences were also evaluated. Sixteen patients were diagnosed with ring-enhancing gliomas, and 15 were diagnosed with intra-axial abscesses. A homogenous signal on T1W (P = 0.049) and T2W (P = 0.042) sequences, a T2W (P = 0.005) or T2*W GE (P = 0.046) peripheral hypointense halo, and an even enhancing capsule (P = 0.002) were significantly associated with brain abscesses. A progressive central enhancement on delayed T1W postcontrast sequences was correlated with ring-enhancing gliomas (P = 0.009). The combination of the following features was suggestive of brain abscess: homogeneous T1W or T2W signal intensity, a T2W or T2*W GE peripheral hypointense halo and an evenly enhancing capsule. Central progression of enhancement on delayed T1W postcontrast sequences was suggestive of glioma.

Transcriptome of microglia reveals a species-specific expression profile in bovines with conserved and new signature genes.

Evidence is growing that microglia adopt different roles than monocyte-derived macrophages (MDM) during CNS injury. However, knowledge about their function in the pathogenesis of neuroinfections is only rudimentary. Cattle are frequently affected by neuroinfections that are either zoonotic or related to diseases in humans, and, hence, studies of bovine neuroinfections as a natural disease model may generate fundamental data on their pathogenesis potentially translatable to humans. We investigated the transcriptomic landscape and lineage markers of bovine microglia and MDM. Although bovine microglia expressed most microglial signature genes known from humans and mice, they exhibited a species-specific transcriptomic profile, including strikingly low expression of TMEM119 and enrichment of the two scavenger receptors MEGF10 and LY75. P2RY12 was amongst the most enriched genes in bovine microglia, and antibodies against P2RY12 labeled specifically resting microglia, but also reactive microglia within neuroinfection foci in-situ. On the other hand, F13A1 was amongst the most enriched genes in bovine monocytes and MDM and, additionally, the encoded protein was expressed in-situ in monocytes and MDM in the inflamed brain but not in microglia, making it a promising marker for infiltrating MDM in the brain. In culture, primary bovine microglia downregulated signature genes, expressed markers of activation, and converged their transcriptome to MDM. However, they retained several microglia signature genes that clearly distinguished them from bovine MDM, making them a promising in-vitro tool to study mechanisms of microglia-pathogen interactions.

A novel Betaretrovirus discovered in cattle with neurological disease and encephalitis.

BACKGROUND: The majority of emerging infectious diseases in humans are of animal origin, and many of them are caused by neuropathogenic viruses. Many cases of neurological disease and encephalitis in livestock remain etiologically unresolved, posing a constant threat to animal and human health. Thus, continuous extension of our knowledge of the repertoire of viruses prone to infect the central nervous system (CNS) is vital for pathogen monitoring and the early detection of emerging viruses. Using high-throughput sequencing (HTS) and bioinformatics, we discovered a new retrovirus, bovine retrovirus CH15 (BoRV CH15), in the CNS of a cow with non-suppurative encephalitis. Phylogenetic analysis revealed the affiliation of BoRV CH15 to the genus Betaretrovirus. RESULTS: BoRV CH15 genomes were identified prospectively and retrospectively by PCR, RT-PCR, and HTS, with targeting of viral RNA and proviral DNA, in six additional diseased cows investigated over a period of > 20 years and of different geographical origins. The virus was not found in brain samples from healthy slaughtered control animals (n = 130). We determined the full-length proviral genomes from six of the seven investigated animals and, using in situ hybridization, identified viral RNA in the cytoplasm of cells morphologically compatible with neurons in diseased brains. CONCLUSIONS: Further screening of brain samples, virus isolation, and infection studies are needed to estimate the significance of these findings and the causative association of BoRV CH15 with neurological disease and encephalitis in cattle. However, with the full-length proviral sequences of BoRV CH15 genomes, we provide the basis for a molecular clone and further in vitro investigation.

Cerebral Ovine Herpesvirus 2 Infection of Cattle Is Associated With a Variable Neuropathological Phenotype.

Cross-species infection with ovine herpesvirus 2 (OvHV-2) in cattle causes malignant catarrhal fever (MCF). MCF may involve the central nervous system (CNS) with necrotizing arteritis and/or vasculitis described to be unique to MCF and discriminatory compared to other viral CNS infections. However, a systematic histopathological characterization of the neural form of MCF in cattle is lacking. We examined medulla oblongata (n = 9) or the entire brain (n = 9) of 18 cattle in which OvHV-2 was identified by quantitative polymerase chain reaction (qPCR), in order to pinpoint potential variations in neuropathology. In 2/18 animals (11%) no lesions were identified, while 16/18 cattle (89%) had brain lesions of varying severity. Presence and quantities of OvHV-2 nucleic acid were determined by in situ hybridization and qPCR, respectively, and were related to the severity of lesions. Fifteen of 18 animals (83%) showed vasculitis, which was mainly of the lymphohistiocytic type, while pathognomonic necrotizing arteritis was only rarely present. Neuroparenchymal lesions included gliosis and/or neuronal changes in 7/16 brains with lesions (44%). The number of CD3+ lymphocytes was highest in animals with simultaneous vascular and neuroparenchymal lesions and high viral genome load. In one animal, OvHV-2 was exclusively observed in CD3+ lymphocytes but not in neurons or microglia. In conclusion, the neuropathological phenotype of bovine MCF in the brain was variable. In some cases, lesions mimicked neurotropic viral encephalitis, while pathognomonic necrotizing arteritis was not a consistent feature of neural MCF. Therefore, molecular detection of OvHV-2 is warranted in the presence of nonsuppurative encephalitis and in the absence of necrotizing arteritis.

Influence of nutrient availability on in vitro growth of major bovine mastitis pathogens.

The aim of the present study was to investigate the effects of milk composition changes on the in vitro growth of bovine mastitis pathogens. Nutritional requirements of three major bovine mastitis pathogens Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Streptococcus uberis (S. uberis) were investigated in vitro. We used ultra-high temperature (UHT) treated milk with different contents of fat, protein, and carbohydrates to test the influence of the availability of various milk constituents on pathogen growth characteristics. Additionally, the bacterial growth was investigated under experimentally modified nutrient availability by dilution and subsequent supplementation with individual nutrients (carbohydrates, different nitrogen sources, minerals, and different types of B vitamins) either to milk or to a conventional medium (thioglycolate broth, TB). Varying contents of fat, protein or lactose did not affect bacterial growth with the exception of growth of S. uberis being promoted in protein-enriched milk. The addition of nutrients to diluted whole milk and TB partly revealed different effects, indicating that there are media-specific growth limiting factors after dilution. Supplementation of minerals to diluted milk did not affect growth rates of all studied bacteria. Bacterial growth in diluted whole milk was decreased by the addition of high concentrations of amino acids in S. aureus, and by urea and additional B vitamins in E. coli and S. aureus. The growth rate of S. uberis was increased by the addition of B vitamins to diluted whole milk. The present results demonstrate that growth-limiting nutrients differ among pathogen types. Because reduced bacterial growth was only shown in diluted milk or TB, it is unlikely that alterations in nutrient availability occurring as a consequence of physiological changes of milk composition in the cow's udder would directly affect the susceptibility or course of bovine mastitis.

CNGB3 Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle.

Sporadic occurrence of inherited eye disorders has been reported in cattle but so far pathogenic variants were found only for rare forms of cataract but not for retinopathies. The aim of this study was to characterize the phenotype and the genetic aetiology of a recessive form of congenital day-blindness observed in several cases of purebred Original Braunvieh cattle. Electroretinography in an affected calf revealed absent cone-mediated function, whereas the rods continue to function normally. Brain areas involved in vision were morphologically normal. When targeting cones by immunofluorescence, a decrease in cone number and an accumulation of beta subunits of cone cyclic-nucleotide gated channel (CNGB3) in the outer plexiform layer of affected animals was obvious. Achromatopsia is a monogenic Mendelian disease characterized by the loss of cone photoreceptor function resulting in day-blindness, total color-blindness, and decreased central visual acuity. After SNP genotyping and subsequent homozygosity mapping with twelve affected cattle, we performed whole-genome sequencing and variant calling of three cases. We identified a single missense variant in the bovine CNGB3 gene situated in a ~2.5 Mb homozygous genome region on chromosome 14 shared between all cases. All affected cattle were homozygous carriers of the p.Asp251Asn mutation that was predicted to be deleterious, affecting an evolutionary conserved residue. In conclusion, we have evidence for the occurrence of a breed-specific novel CNGB3-related form of recessively inherited achromatopsia in Original Braunvieh cattle which we have designated OH1 showing an allele frequency of the deleterious allele of ~8%. The identification of carriers will enable selection against this inherited disorder. The studied cattle might serve as an animal model to further elucidate the function of CNGB3 in mammals.

Vertebral fracture due to Actinobacillus pleuropneumoniae osteomyelitis in a weaner.

BACKGROUND: Osteomyelitis is relatively frequent in young pigs and a few bacterial species have been postulated to be potential causative agents. Although Actinobacillus (A.) pleuropneumoniae has been sporadically described to cause osteomyelitis, typically, actinobacillosis is characterized by respiratory symptoms. Nevertheless, subclinical infections are a challenging problem in pig herds. To the authors' knowledge, this is the first case description that reports clinical, diagnostic imaging, pathological and histopathological findings of vertebral osteomyelitis in a pig and first describes A. pleuropneumoniae as the causative agent identified by advanced molecular methods. CASE PRESENTATION: An eight-week-old female weaner was presented with a non-ambulatory tetraparesis. The neurological signs were consistent with a lesion in the C6-T2 spinal cord segments. Imaging studies revealed a collapse of the seventh cervical vertebral body (C7) with a well demarcated extradural space-occupying mass ventrally within the vertebral canal severely compressing the spinal cord. Post-mortem examination identified an abscess and osteomyelitis of C7 and associated meningitis and neuritis with subsequent pathological fracture of C7 and compression of the spinal cord. In the microbiological analysis, A. pleuropneumoniae was identified using PCR and DNA sequence analysis. CONCLUSIONS: A. pleuropneumoniae can be responsible for chronic vertebral abscess formation with subsequent pathological fracture and spinal cord compression in pigs.

Diffuse Leptomeningeal Oligodendrogliomatosis in a Cow.

A 4.5-year-old cow showing neurological signs consistent with predictors of bovine spongiform encephalopathy (BSE) was investigated as a potential BSE-suspect case and proved to be negative. Macroscopic analysis revealed a tan neoplastic mass growing along the leptomeninges of the caudal brain and extending into the third (III) ventricle without significantly involving the neuroparenchyma. Pathological features (uniform round hyperchromatic neoplastic cells embedded in abundant myxoid matrix, microcysts, microvascular proliferation) and diffuse Olig2 expression were most consistent with diffuse high-grade leptomeningeal oligodendrogliomatosis. In line with former reports of extensive leptomeningeal involvement in bovine oligodendroglioma, this report suggests that bovine oligodendroglial tumors have a strong propensity to grow within the leptomeningeal space. In addition, it indicates that Olig2 is a useful marker to confirm glial lineage in formalin-fixed, paraffin-embedded bovine tissue.

Inter- and Intraobserver Agreement of Canine and Feline Nervous System Tumors.

In routine diagnostic activity, pathologists may be confronted with nervous system tumors. The lack of clinical information, economic restrictions for additional testing, and the lack of expertise in neuropathology may render the diagnosis challenging. The goals of this study were to assess the agreement in diagnosing nervous system tumors in domestic carnivores among 4 board-certified surgical pathologists without particular expertise in neuropathology and a neuropathologist expert, and to investigate the utility of special stains frequently used in routine diagnostic laboratories. Forty-six tumors (7 cats, 38 dogs, and 1 unknown carnivore) were retrieved and 1 hematoxylin and eosin-stained slide per tumor was selected. Diagnoses (tumor type and subtype) were formulated based on histological features and available clinical information. Confidence in the diagnosis was also scored. Subsequently, a panel of histochemical and immunohistochemical stains (Gordon Sweet silver stain and immunohistochemistry for AE1/AE3, vimentin, glial fibrillary acid protein, S100, neuron-specific enolase and neurofilament) was evaluated by the pathologists, who either confirmed or changed their original diagnoses. Intraobserver and interobserver agreement and confidence in relation to diagnosis before and after analysis of special stains were assessed. The use of special stains increased the complete agreement among surgical pathologists, with regard to tumor type, from 63% to 74%. Cases with a high confidence score had a higher interobserver agreement than cases with a low confidence score. These results suggest that pathologists without expertise in neuropathology agree in the diagnosis of most nervous system tumors, and special stains available in most laboratories only slightly increase this agreement.

Correction: Hairless Streaks in Cattle Implicate TSR2 in Early Hair Follicle Formation.

[This corrects the article DOI: 10.1371/journal.pgen.1005427.].

Metabolic profiling of listeria rhombencephalitis in small ruminants by 1 H high-resolution magic angle spinning NMR spectroscopy.

Listeria rhombencephalitis is caused by infection with Listeria monocytogenes and is associated with a high mortality rate in humans and ruminants. Little is known about the metabolic changes associated with neurolisteriosis in particular and infectious central nervous system (CNS) diseases in general. The purpose of our study was to investigate the metabolic changes associated with listeria rhombencephalitis in small ruminants (goats and sheep) as a model for inflammatory CNS disease by 1 H high-resolution magic angle spinning nuclear magnetic resonance (1 H HR-MAS NMR) spectroscopy of brain biopsies obtained from the brainstem and thalamus. Statistical analysis revealed distinct differences in the metabolic profile of brainstem biopsies, the primary location of listeria rhombencephalitis with moderate or severe inflammatory changes. N-Acetylaspartate (NAA), N-acetylaspartylglutamate, choline, myo-inositol and scyllo-inositol were decreased, and glycine, phosphocholine, taurine and lactate were increased, in the diseased group (n = 13) in comparison with the control group (n = 12). In the thalamus, which showed no or only mild inflammatory changes in the majority of animals, no statistically significant metabolic changes were observed. However, trends for metabolic alterations were partly the same as those found in the brainstem, including NAA, choline and lactate. This may be an indicator of metabolic changes occurring in the early stages of the disease. Therefore, further research with a larger number of animals is needed to evaluate the presence of subtle metabolic changes associated with mild inflammatory changes in the thalamus. In conclusion, 1 H HR-MAS NMR investigation of listeria rhombencephalitis identified brain metabolite changes, offering new insights into the disease pathophysiology.