Primary and secondary leptomeningeal gliomatosis in dogs.

Leptomeningeal gliomatosis (LG) is characterized by extensive dissemination of neoplastic glial cells in the subarachnoid space either without an intraparenchymal glioma (primary LG or PLG) or secondary to an intraparenchymal glioma (secondary LG or SLG). Given the low frequency of LG in human and veterinary medicine, specific diagnostic criteria are lacking. Here, we describe 14 cases of canine LG that were retrospectively identified from 6 academic institutions. The mean age of affected dogs was 7.3 years and over 90% of patients were brachycephalic. Clinical signs were variable and progressive. Relevant magnetic resonance image findings in 7/14 dogs included meningeal enhancement of affected areas and/or intraparenchymal masses. All affected dogs were euthanized because of the poor prognosis. Gross changes were reported in 12/14 cases and consisted mainly of gelatinous leptomeningeal thickening in the brain (6/12 cases) or spinal cord (2/12 cases) and 1 or multiple, gelatinous, gray to red intraparenchymal masses in the brain (6/12 cases). Histologically, all leptomeningeal neoplasms and intraparenchymal gliomas were morphologically consistent with oligodendrogliomas. Widespread nuclear immunolabeling for OLIG2 was observed in all neoplasms. The absence of an intraparenchymal glioma was consistent with PLG in 3 cases. The remaining 11 cases were diagnosed as SLG.

Miliary osteoma cutis in a climbing mantella frog (Mantella laevigata).

A climbing mantella frog (Mantella laevigata) was presented with nodular thickened skin. Histological examination revealed dermal nodules composed of differentiated bone consistent with miliary osteoma cutis, a non-neoplastic condition where bone is abnormally deposited within the skin. This is the first report of idiopathic osteoma cutis in an amphibian.

High-Grade, Stage 2 Mast Cell Tumors: Outcome in Dogs With Local and Systemic Therapy.

Canine mast cell tumors (MCTs) have highly variable clinical behavior, and predicting outcomes in individual dogs remains challenging. Many studies combine dogs with varying tumor grades, clinical stage, or treatments, confounding those results. The purpose of this retrospective study was to determine outcome and prognostic factors in a specific subset of dogs with high-grade, stage 2, cutaneous MCTs treated with adequate local control via surgery with or without radiation therapy and adjuvant cytotoxic chemotherapy. Seventeen dogs met the inclusion criteria, and the median survival time was 259 days. Development of local recurrence, tumor location, and presence of ulceration were all associated with shorter survival times. Tumor size, mitotic count, chemotherapy protocol, lymph node classification, and radiation therapy were not significantly associated with outcome. In this study, a specific population of dogs characterized by high-grade MCTs with local lymph node metastasis who received aggressive local and systemic therapy had a median survival of about 8.5 mo. Dogs with ulcerated tumors, recurrent tumors, or tumors located on the head had a worse outcome despite aggressive therapy. These results may serve as a basis of comparison for future research exploring alternative treatment combinations in this specific population of dogs.

IDH1 mutant glioma is preferentially sensitive to the HDAC inhibitor panobinostat.

INTRODUCTION: A large subset of diffusely infiltrative gliomas contains a gain-of-function mutation in isocitrate dehydrogenase 1 or 2 (IDH1/2mut) which produces 2-hydroxglutarate, an inhibitor of α-ketoglutarate-dependent DNA demethylases, thereby inducing widespread DNA and histone methylation. Because histone deacetylase (HDAC) enzymes are localized to methylated chromatin via methyl-binding domain proteins, IDH1/2mut gliomas may be more dependent on HDAC activity, and therefore may be more sensitive to HDAC inhibitors. METHODS: Six cultured patient-derived glioma cell lines, IDH1wt (n = 3) and IDH1mut (n = 3), were treated with an FDA-approved HDAC inhibitor, panobinostat. Cellular cytotoxicity and proliferation assays were conducted by flow cytometry. Histone modifications and cell signaling pathways were assessed using immunoblot and/or ELISA. RESULTS: IDH1mut gliomas exhibited marked upregulation of genes associated with the HDAC activity. Glioma cell cultures bearing IDH1mut were significantly more sensitive to the cytotoxic and antiproliferative effects of panobinostat, compared to IDH1wt glioma cells. Panobinostat caused a greater increase in acetylation of the histone residues H3K14, H3K18, and H3K27 in IDH1mut glioma cells. Another HDAC inhibitor, valproic acid, was also more effective against IDH1mut glioma cells. CONCLUSION: These data suggest that IDH1mut gliomas may be preferentially sensitive to HDAC inhibitors. Further, IDH1mut glioma cultures showed enhanced accumulation of acetylated histone residues in response to panobinostat treatment, suggesting a direct epigenetic mechanism for this sensitivity. This provides a rationale for further exploration of HDAC inhibitors against IDH1mut gliomas.

Comparative Pathology of the Peripheral Nervous System.

The peripheral nervous system (PNS) relays messages between the central nervous system (brain and spinal cord) and the body. Despite this critical role and widespread distribution, the PNS is often overlooked when investigating disease in diagnostic and experimental pathology. This review highlights key features of neuroanatomy and physiology of the somatic and autonomic PNS, and appropriate PNS sampling and processing techniques. The review considers major classes of PNS lesions including neuronopathy, axonopathy, and myelinopathy, and major categories of PNS disease including toxic, metabolic, and paraneoplastic neuropathies; infectious and inflammatory diseases; and neoplasms. This review describes a broad range of common PNS lesions and their diagnostic criteria and provides many useful references for pathologists who perform PNS evaluations as a regular or occasional task in their comparative pathology practice.

BRD4 is associated with raccoon polyomavirus genome and mediates viral gene transcription and maintenance of a stem cell state in neuroglial tumour cells.

Polyomavirus infection often results in persistence of the viral genome with little or no virion production. However, infection of certain cell types can result in high viral gene transcription and either cytolysis or neoplastic transformation. While infection by polyomavirus is common in humans and many animals, major questions regarding viral persistence of most polyomaviruses remain unanswered. Specifically, identification of target cells for viral infection and the mechanisms polyomaviruses employ to maintain viral genomes within cells are important not only in ascribing causality to polyomaviruses in disease, but in understanding specific mechanisms by which they cause disease. Here, we characterize the cell of origin in raccoon polyomavirus (RacPyV)-associated neuroglial brain tumours as a neural stem cell. Moreover, we identify an association between the viral genome and the host cell bromodomain protein, BRD4, which is involved in numerous cellular functions, including cell cycle progression, differentiation of stem cells, tethering of persistent DNA viruses, and regulation of viral and host-cell gene transcription. We demonstrate that inhibition of BRD4 by the small molecule inhibitors (+)-JQ1 and IBET-151 (GSK1210151A) results in reduced RacPyV genome within cells in vitro, as well as significant reduction of viral gene transcripts LT and VP1, highlighting its importance in both maintenance of the viral genome and in driving oncogenic transformation by RacPyV. This work implicates BRD4 as a central protein involved in RacPyV neuroglial tumour cell proliferation and in the maintenance of a stem cell state.

The raccoon polyomavirus genome and tumor antigen transcription are stable and abundant in neuroglial tumors.

UNLABELLED: Raccoon polyomavirus (RacPyV) is associated with 100% of neuroglial tumors in free-ranging raccoons. Other tumor-associated polyomaviruses (PyVs), including simian virus 40 (SV40), murine PyV, and Merkel cell PyV, are found integrated in the host genome in neoplastic cells, where they constitutively express splice variants of the tumor antigen (TAg) gene. We have previously reported that RacPyV exists only as an episome (nonintegrated) in neuroglial tumors. Here, we have investigated TAg transcription in primary tumor tissue by transcriptome analysis, and we identified the alternatively spliced TAg transcripts for RacPyV. We also determined that TAg was highly transcribed relative to host cellular genes. We further colocalized TAg DNA and mRNA by in situ hybridization and found that the majority of tumor cells showed positive staining. Lastly, we examined the stability of the viral genome and TAg transcription by quantitative reverse transcriptase PCR in cultured tumor cells in vitro and in a mouse xenograft model. When tumor cells were cultured in vitro, TAg transcription increased nearly 2 log-fold over that of parental tumor tissue by passage 17. Both episomal viral genome and TAg transcription were faithfully maintained in culture and in tumors arising from xenotransplantation of cultured cells in mice. This study represents a minimal criterion for RacPyV's association with neuroglial tumors and a novel mechanism of stability for a polyomavirus in cancer. IMPORTANCE: The natural cycle of polyomaviruses in mammals is to persist in the host without causing disease, but they can cause cancer in humans or in other animals. Because this is an unpredictable and rare event, the oncogenic potential of polyomavirus is primarily evaluated in laboratory animal models. Recently, raccoon polyomavirus (RacPyV) was identified in neuroglial tumors of free-ranging raccoons. Viral copy number was consistently high in these tumors but was low or undetectable in nontumor tissue or in unaffected raccoons. Unlike other oncogenic polyomaviruses, RacPyV was episomal, not integrated, in these tumors. To determine the stability of the viral genome and sustained transcription of the oncogenic tumor antigen genes, we cultured primary raccoon tumor cells and passaged them in mice, confirming the nonintegrated state of the virus and the maintenance of viral gene transcription throughout. RacPyV provides a naturally occurring and tractable model for a novel mechanism of polyomavirus-mediated oncogenesis.

Equine neuroaxonal dystrophy/degenerative myeloencephalopathy in Gypsy Vanner horses.

BACKGROUND: Equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disease that primarily affects young, genetically predisposed horses that are deficient in vitamin E. Equine NAD/EDM has not previously been documented in Gypsy Vanner horses (GVs). OBJECTIVES: To evaluate: (1) the clinical phenotype, blood vitamin E concentrations before and after supplementation and pedigree in a cohort of GV horses with a high prevalence of neurologic disease suspicious for eNAD/EDM and (2) to confirm eNAD/EDM in GVs through postmortem evaluation. ANIMALS: Twenty-six GVs from 1 farm in California and 2 cases from the Midwestern U.S. METHODS: Prospective observational study on Californian horses; all 26 GVs underwent neurologic examination. Pre-supplementation blood vitamin E concentration was assessed in 17- GVs. Twenty-three were supplemented orally with 10 IU/kg of liquid RRR-alpha-tocopherol once daily for 28 days. Vitamin E concentration was measured in 23 GVs after supplementation, of which 15 (65%) had pre-supplementation measurements. Two clinically affected GVs from California and the 2 Midwestern cases had necropsy confirmation of eNAD/EDM. RESULTS: Pre-supplementation blood vitamin E concentration was ≤2.0 µg/mL in 16/17 (94%) of GVs from California. Post-supplementation concentration varied, with a median of 3.39 µg/mL (range, 1.23-13.87 µg/mL), but only 12/23 (52%) were normal (≥3.0 µg/mL). Normalization of vitamin E was significantly associated with increasing age (P = .02). Euthanized horses (n = 4) had eNAD/EDM confirmed at necropsy. CONCLUSIONS AND CLINICAL IMPORTANCE: GVs could have a genetic predisposition to eNAD/EDM. Vitamin E supplementation should be considered and monitored in young GVs.

Neurodegeneration in a domestic rabbit with severe malnourishment and low hepatic copper.

Copper is a trace element that plays an essential role in neurodevelopment and neurologic function. Acquired copper deficiency has a range of neurologic manifestations, with myelopathy being the most common association. We describe here the clinical, radiologic, histopathologic, and toxicologic findings of a rabbit with malnutrition, neurodegeneration, and suspected copper deficiency. A stray, adult female dwarf rabbit cross (Oryctolagus cuniculus) in poor body condition developed ataxia and pelvic limb weakness progressing to lateral recumbency and urine retention. The clinical findings suggested multifocal brainstem disease with right-sided central vestibular involvement; however, microscopic examination identified thoracic and lumbosacral spinal cord myelopathy. Differentials for the spinal cord changes included neurodegenerative disease, nutritional deficiency, neurotoxin, trauma to the lumbosacral region, and ischemia. Hepatic copper levels were suboptimal at 18 ppm dry weight (RI: 24-150 ppm dry weight). While speculative, copper-deficiency myelopathy is a treatable cause of non-compressive myelopathy that may occur in this species.

Clinicopathological and pedigree investigation of a novel spinocerebellar neurological disease in juvenile Quarter Horses in North America.

BACKGROUND: In 2020, a novel neurologic disease was observed in juvenile Quarter Horses (QHs) in North America. It was unknown if this was an aberrant manifestation of another previously described neurological disorder in foals, such as equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM). HYPOTHESIS/OBJECTIVES: To describe the clinical findings, outcomes, and postmortem changes with Equine Juvenile Spinocerebellar Ataxia (EJSCA), differentiate the disease from other similar neurological disorders, and determine a mode of inheritance. ANIMALS: Twelve neurologically affected QH foals and the dams. METHODS: Genomic DNA was isolated and pedigrees were manually constructed. RESULTS: All foals (n = 12/12) had a history of acute onset of neurological deficits with no history of trauma. Neurological deficits were characterized by asymmetrical spinal ataxia, with pelvic limbs more severely affected than thoracic limbs. Clinicopathological abnormalities included high serum activity of gamma-glutamyl transferase and hyperglycemia. All foals became recumbent (median, 3 days: [0-18 days]), which necessitated humane euthanasia (n = 11/12, 92%; the remaining case was found dead). Histological evaluation at postmortem revealed dilated myelin sheaths and digestion chambers within the spinal cord, most prominently in the dorsal spinocerebellar tracts. Pedigree analysis revealed a likely autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: EJSCA is a uniformly fatal, rapidly progressive, likely autosomal recessive neurological disease of QHs <1 month of age in North America that is etiologically distinct from other clinically similar neurological disorders. Once the causative variant for EJSCA is validated, carriers can be identified through genetic testing to inform breeding decisions.

Lung and lymph node explants to study the interaction between host cells and canine distemper virus.

Canine distemper virus (CDV, family Paramyxoviridae) is a widely known fatal disease in unvaccinated dogs and wild carnivores. The virus enters via the respiratory tract and rapidly spreads to the lymphoid organs. To investigate viral entry into these tissues, a dog tissue explant model was developed for lung and lymph nodes. Canine lung explants were cultured with CDV for three days. During this time CDV antigens were visible on alveolar cells, which were CD163-positive and SLAM-positive (signaling lymphocytic activation molecule), demonstrating that they were macrophages. The lymph node explants were maintained for five days. During this time the viral replication increased progressively by each day post infection and syncytia were observed by day three, post exposure. The microscopic distribution of CDV-positive cells in the lymph nodes, including the syncytia, and co-expression of CD163 and SLAM, demonstrated that they were macrophages. These findings suggest that alveolar macrophages are the first cells in the lung to become infected during CDV infection, and lymph node explants showed similar replication rates and virus-cell interactions as seen in experimental live animals. This demonstrates the utility of canine respiratory and lymphoid explant model to evaluate cell entry and viral replication of CDV and other morbilliviruses in dogs or other susceptible carnivores.

Fatal balamuthosis in a Siberian tiger and a literature review of detection options for free-living amoebic infections in animals.

Free-living amoebae are rare causes of morbidity and mortality in humans and animals around the globe. Because the route of exposure and clinical progression of disease caused by different species of amoebae may vary in people and animals, determining the species of amoeba present is important. We describe here a fatal infection by the free-living amoeba Balamuthia mandrillaris in a Siberian tiger (Panthera tigris altaica). The 17-y-old patient had a rapid clinical decline after a peracute onset of severe lethargy, dull mentation, and anorexia. Autopsy did not identify a cause of death. Histology revealed inflammation associated with amoebic trophozoites in the brain, lungs, and iris of one eye. These amoebae were confirmed to be B. mandrillaris based on a PCR assay and sequencing. Although there are subtle morphologic differences between cyst stages of Acanthamoeba spp., B. mandrillaris, and Naegleria fowleri when present and identified on routine staining, other modalities, including PCR, immunofluorescence, electron microscopy, and immunohistochemistry, are typically utilized to confirm the pathogen involved in these cases. We review the reports of balamuthosis in animals.

Oculosystemic pneumocystosis in 2 sibling Chihuahuas.

Sibling female and male Chihuahuas were evaluated for a 9-month history of tachypnea that failed to respond to fenbendazole, doxycycline, amoxicillin-clavulanate, and prednisone. Physical examination identified tachypnea, hyperpnea, and harsh bronchovesicular lung sounds. Fundic examination disclosed diffuse chorioretinitis, manifested as multifocal chorioretinal granulomas in the female dog and occasional chorioretinal scars in the male dog. Thoracic radiographs indicated moderate to severe interstitial to broncho-interstitial infiltrates in both dogs. Serum and urine antigen and antibody testing in the female dog failed to identify infectious agents, but cytologic assessment of hepatic lymph node, liver, and splenic aspirates identified Pneumocystis trophozoites. Infection was confirmed in both dogs by 28S rRNA PCR sequencing from multiple tissue samples. The female dog responded well to trimethoprim-sulfamethoxazole, but the male dog was euthanized because of liver failure, presumably related to antimicrobial treatment.

Intra- and Intertumoral Microglia/Macrophage Infiltration and Their Associated Molecular Signature Is Highly Variable in Canine Oligodendroglioma: A Preliminary Evaluation.

The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the intratumoral concentration of several known GAM-derived pro-tumorigenic molecules in high-grade oligodendrogliomas compared to that in a normal brain. Our analysis demonstrated marked intra- and intertumoral heterogeneity of GAM infiltration. Correspondingly, we observed significant variability in the intratumoral concentrations of several GAM-associated molecules, unlike what we previously observed in high-grade astrocytomas. However, high-grade oligodendroglioma tumor homogenates (n = 6) exhibited an increase in the pro-tumorigenic molecules hepatocyte growth factor receptor (HGFR) and vascular endothelial growth factor (VEGF), as we observed in high-grade astrocytomas. Moreover, neoplastic oligodendrocytes displayed robust expression of GAL-3, a chimeric galectin implicated in driving immunosuppression in human glioblastoma. While this work identifies shared putative therapeutic targets across canine glioma subtypes (HGFR, GAL-3), it highlights several key differences in the immune landscape. Therefore, a continued effort to develop a comprehensive understanding of the immune microenvironment within each subtype is necessary to inform therapeutic strategies going forward.

Genetic evidence for the role of Erk activation in a lymphoproliferative disease of mice.

Germline mutation of the linker for activation of T cells (LAT) gene at the phospholipase C-gamma1 (PLC-gamma1)-binding site leads to a fatal lymphoproliferative disease in mice. The hyperactivated T cells that develop in these mice have defective T-cell antigen receptor (TCR)-induced calcium flux but enhanced mitogen-activated protein kinase (MAPK) activation. We used genetic analysis to investigate genes whose products might suppress MAPK activation and lymphoproliferative disease in LAT mutant mice. B-lymphocyte adaptor molecule of 32 kDa (Bam32) is a known mediator of MAPK activation in B cells. We recently reported that in CD4(+) T cells, Bam32 deficiency decreased MAPK activation and specifically extracellular-signal-regulated kinase (Erk) signaling, following TCR stimulation. By crossing the Bam32 null mutation onto the LAT knock-in background, we found that the Bam32 null mutation delayed the onset and decreased the severity of lymphoproliferative disease in LAT knock-in mice. The pulmonary lymphocyte infiltration seen in LAT knock-in mice was also markedly decreased in double-mutant mice. Additionally, Erk activation was diminished in LAT knock-in Bam32 knockout CD4(+) T cells. To more accurately determine the role of Erk in this delay of lymphoproliferative disease, we also bred a transgenic, hypersensitive Erk allele (the Erk2 sevenmaker mutant) onto the LAT knock-in Bam32 knockout double-mutant background. These triple transgenic mice demonstrated a role for Erk activation in lymphoproliferative disease caused by the LAT knock-in mutation.

R132H IDH1 sensitizes glioma to the antiproliferative and cytotoxic effects of BET inhibition.

INTRODUCTION: Mutations in isocitrate dehydrogenase 1/2 (IDHmut) identify a subset of gliomas that exhibit epigenetic dysregulation via aberrant DNA methylation. These tumors are ultimately fatal and lack effective therapeutic strategies. Considering the epigenetic dysregulation of IDHmut gliomas, we hypothesized that epigenetic-targeting drugs may yield therapeutic benefits in gliomas bearing IDHmut. One set of targets includes the bromodomain and extraterminal (BET) family of transcriptional coactivators. METHODS: We used TCGA data from glioma patients to determine whether BET proteins affect patient survival differently based on IDH status. Follow-up experiments using a set of IDH wildtype/mutant glioma cultures, as well as an IDH wildtype glioblastoma cell line expressing exogenous R132H IDH1, focused on cell health assays to investigate whether IDHmut was associated with increased sensitivity to the BET inhibitor JQ1. Immunoblots were used to evaluate the molecular response to JQ1 in these cultures. RESULTS: We identified that high BRD4 expression associated with decreased survival only in IDHmut glioma patients. Cell viability analysis showed that IDHmut sensitized glioma cells to delayed cytotoxicity (10 days) in response to JQ1. Early effects of JQ1 (3 days) were primarily antiproliferative, with IDHmut glioma exhibiting a modest increase in sensitivity. Finally, exogenous R132H IDH1 expression in a resistant IDH wildtype cell line recapitulated the JQ1-mediated delayed cytotoxicity seen in our endogenous IDHmut glioma cells. CONCLUSION: Overall, these data suggest that BRD4 enhances malignancy primarily in gliomas bearing IDHmut and is associated with greater sensitivity to BET inhibition. The finding that BET inhibition primarily exhibits delayed cytotoxicity may be overlooked in conventional short endpoint dose-response assays. Follow-up mechanistic and animal studies will help address the translational potential of these findings.

Case series: Pleural effusion caused by urinary ultrafiltrate in two cats without evidence of urinary obstruction, trauma, or simultaneous perinephric pseudocysts.

Objectives: To describe the diagnostic techniques, surgical treatments, and outcomes of two cats with recurrent pleural transudate caused by urinary ultrafiltrate. Animals: Two cats without evidence of trauma, urinary tract obstruction, or concurrent perinephric pseudocysts that were evaluated and treated for recurrent pleural transudate caused by urinary ultrafiltrate. Study design: Short case series. Methods: Multiphase contrast CT scan revealed leakage of contrast media from the kidneys bilaterally into the retroperitoneal spaces in both cats. Renal scintigraphy performed in one cat revealed progressive accumulation of 99mTc diethylenetriamine penta-acetic acid (Tc-DTPA) in the pleural space. Exploratory laparotomy localized the leakage of fluid to renal capsular defects bilaterally in both cats. The retroperitoneum was incised bilaterally to promote fluid drainage into the peritoneum, and nephropexies were performed. Results: One cat had long-term survival with recurrent, though decreasing volumes of, pleural effusion. The second cat was euthanized 16 days postoperatively for progressive renal disease. Conclusion: The diagnosis of spontaneous urinary ultrafiltrate accumulation in the pleural space of cats without evidence of trauma, urinary tract obstruction, or concurrent perinephric pseudocysts has not previously been reported. The surgical correction described reduced but did not completely eliminate the rate of pleural effusion accumulation.

Case Report: MRI, Clinical, and Pathological Correlates of Bromethalin Toxicosis in Three Dogs.

Bromethalin toxicosis is an increasingly common clinical presentation in dogs that may be fatal depending on the extent of intoxication. Antemortem diagnosis of bromethalin toxicosis was achieved in three dogs by demonstration of the active metabolite desmethylbromethalin in fat or serum. Magnetic resonance imaging (MRI) findings were consistent with a diffuse leukoencephalopathy with restricted diffusion and prominent involvement of the corticospinal motor tracts on T2-weighted and diffusion-weighted sequences. Imaging findings were confirmed in one non-surviving dog at necropsy. Resolution of MRI abnormalities was demonstrated in one surviving dog that was consistent with the associated resolution of clinical signs. Initial findings in these dogs support further investigation of specific MRI patterns in cases of leukoencephalopathy to aid differential diagnosis. While antemortem detection of bromethalin and its metabolites confirms exposure, quantitation may be informative as a prognostic biomarker.

Postmortem diagnoses of spinal ataxia in 316 horses in California.

OBJECTIVE: To determine period prevalences of postmortem diagnoses for spinal cord or vertebral column lesions as underlying causes of ataxia (spinal ataxia) in horses. ANIMALS: 2,861 client-owned horses (316 with ataxia [ataxic group] and 2,545 without ataxia [control group]). PROCEDURES: The medical records database of the University of California-Davis Veterinary Medical Teaching Hospital was searched to identify horses necropsied between January 1, 2005, and December 31, 2017. Results were compared between the ataxic and control groups and between various groups of horses in the ataxic group. Period prevalences were determined for the most common causes of ataxia. RESULTS: 2,861 horses underwent full necropsy, and the period prevalences for the most common definitive diagnoses for ataxia were 2.7% (77/2,861) for cervical vertebral compressive myelopathy (CVCM), 1.3% (38/2,861) for equine neuroaxonal dystrophy or equine degenerative myeloencephalopathy (eNAD-EDM), and 0.9% (25/2,861) for trauma; the period prevalence of ataxia of unknown origin was 2.0% (56/2,861). Horses in the ataxic group (vs the control group) were more likely to have been warmblood horses (OR, 2.70) and less likely to have been Arabian horses (OR, 0.53). In the ataxic group, horses < 5 (vs ≥ 5) years of age had greater odds of CVCM (OR, 2.82) or eNAD-EDM (OR, 6.17) versus trauma or ataxia of unknown origin. Horses in the ataxic group with CVCM were more likely Thoroughbreds (OR, 2.54), whereas horses with eNAD-EDM were more likely American Quarter Horses (OR, 2.95) and less likely Thoroughbreds (OR, 0.11). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that breed distributions differed for horses with CVCM versus eNAD-EDM; therefore, breed should be considered in the clinical evaluation of spinal ataxia in horses.

A comparative analysis of two unrelated outbreaks in Latvia and Australia of acquired idiopathic megaesophagus in dogs fed two brands of commercial dry dog foods: 398 cases (2014-2018).

CASE DESCRIPTION: In Latvia in 2014, acquired idiopathic megaesophagus (AIME) was observed in increased numbers of dogs that consumed varieties of 1 brand of dog food. Within 2 years, 253 dogs were affected. In Australia in November 2017, 6 working dogs that consumed 1 diet of another brand of dog food developed AIME. In total, 145 Australian dogs were affected. CLINICAL FINDINGS: AIME was diagnosed predominantly in large-breed male dogs (> 25 kg [55 lb]). Regurgitation, weight loss, and occasionally signs consistent with aspiration pneumonia (coughing, dyspnea, or fever) were noted. Most Latvian dogs had mild to severe peripheral polyneuropathies as evidenced by laryngeal paralysis, dysphonia, weakness, and histopathologic findings consistent with distal axonopathy. In Australian dogs, peripheral polyneuropathies were not identified, and histopathologic findings suggested that the innervation of the esophagus and pharynx was disrupted locally, although limited samples were available. TREATMENT AND OUTCOME: Investigations in both countries included clinical, epidemiological, neuropathologic, and case-control studies. Strong associations between the dog foods and the presence of AIME were confirmed; however, toxicological analyses did not identify a root cause. In Latvia, the implicated dietary ingredients and formulations were unknown, whereas in Australia, extensive investigations were conducted into the food, its ingredients, the supply chain, and the manufacturing facilities, but a cause was not identified. CLINICAL RELEVANCE: A panel of international multidisciplinary experts concluded that the cause of AIME in both outbreaks was likely multifactorial, with the possibility of individualized sensitivities. Without a sentinel group, the outbreak in Australia may not have been recognized for months to years, as happened in Latvia. A better surveillance system for early identification of pet illnesses, including those associated with pet foods, is needed.