Brian F. Porter

MAGNETIC RESONANCE IMAGING FEATURES OF INTRACRANIAL ASTROCYTOMAS AND OLIGODENDROGLIOMAS IN DOGS

Astrocytomas and oligodendrogliomas represent one third of histologically confirmed canine brain tumors. Our purpose was to describe the magnetic resonance (MR) imaging features of histologically confirmed canine intracranial astrocytomas and oligodendrogliomas and to examine for MR features that differentiate these tumor types. Thirty animals with confirmed astrocytoma (14) or oligodendroglioma (16) were studied. All oligodendrogliomas and 12 astrocytomas were located in the cerebrum or thalamus, with the remainder of astrocytomas in the cerebellum or caudal brainstem. Most (27/30) tumors were associated with both gray and white matter. The signal characteristics of both tumor types were hypointense on T1-weighted images (12 each) and hyperintense on T2-weighted images (11/14 astrocytomas, 12/16 oligodendrogliomas). For astrocytomas and oligodendrogliomas, respectively, common findings were contrast enhancement (10/13, 11/15), ring-like contrast enhancement (6/10, 9/11), cystic regions within the mass (7/14, 12/16), and hemorrhage (4/14, 6/16). Oligodendrogliomas were significantly more likely to contact the brain surface (meninges) than astrocytomas (14/16, 7/14, respectively, P=0.046). Contact with the lateral ventricle was the most common finding, occurring in 13/14 astrocytomas and 14/16 oligodendrogliomas. No MR features were identified that reliably distinguished between these two tumor types. Contrast enhancement was more common in high-grade tumors (III or IV) than low-grade tumors (II, P=0.008).

Naturally Occurring Disk Herniation in Dogs: An Opportunity for Pre-Clinical Spinal Cord Injury Research

Traumatic spinal cord injuries represent a significant source of morbidity in humans. Despite decades of research using experimental models of spinal cord injury to identify candidate therapeutics, there has been only limited progress toward translating beneficial findings to human spinal cord injury. Thoracolumbar intervertebral disk herniation is a naturally occurring disease that affects dogs and results in compressive/contusive spinal cord injury. Here we discuss aspects of this disease that are analogous to human spinal cord injury, including injury mechanisms, pathology, and metrics for determining outcomes. We address both the strengths and weaknesses of conducting pre-clinical research in these dogs, and include a review of studies that have utilized these animals to assess efficacy of candidate therapeutics. Finally, we consider a two-species approach to pre-clinical data acquisition, beginning with a reproducible model of spinal cord injury in the rodent as a tool for discovery with validation in pet dogs with intervertebral disk herniation.

Evaluation of brain tissue or cerebrospinal fluid with broadly reactive polymerase chain reaction for Ehrlichia, Anaplasma, spotted fever group Rickettsia, Bartonella, and Borrelia species in canine neurological diseases (109 cases).

BACKGROUND Vector-transmitted microorganisms in the genera Ehrlichia, Anaplasma, Rickettsia, Bartonella, and Borrelia are commonly suspected in dogs with meningoencephalomyelitis (MEM), but the prevalence of these pathogens in brain tissue and cerebrospinal fluid (CSF) of dogs with MEM is unknown. HYPOTHESIS/OBJECTIVES To determine if DNA from these genera is present in brain tissue and CSF of dogs with MEM, including those with meningoencephalitis of unknown etiology (MUE) and histopathologically confirmed cases of granulomatous (GME) and necrotizing meningoencephalomyelitis (NME). ANIMALS Hundred and nine dogs examined for neurological signs at 3 university referral hospitals. METHODS Brain tissue and CSF were collected prospectively from dogs with neurological disease and evaluated by broadly reactive polymerase chain reaction (PCR) for Ehrlichia, Anaplasma, Spotted Fever Group Rickettsia, Bartonella, and Borrelia species. Medical records were evaluated retrospectively to identify MEM and control cases. RESULTS Seventy-five cases of MUE, GME, or NME, including brain tissue from 31 and CSF from 44 cases, were evaluated. Brain tissue from 4 cases and inflammatory CSF from 30 cases with infectious, neoplastic, compressive, vascular, or malformative disease were evaluated as controls. Pathogen nucleic acids were detected in 1 of 109 cases evaluated. Specifically, Bartonella vinsonii subsp. berkhoffii DNA was amplified from 1/6 dogs with histopathologically confirmed GME. CONCLUSION AND CLINICAL IMPORTANCE The results of this investigation suggest that microorganisms in the genera Ehrlichia, Anaplasma, Rickettsia, and Borrelia are unlikely to be directly associated with canine MEM in the geographic regions evaluated. The role of Bartonella in the pathogenesis of GME warrants further investigation.

Epidemiology of Necrotizing Meningoencephalitis in Pug Dogs

Background: Although the histopathologic features of necrotizing meningoencephalitis (NME) have been described previously, little information is available concerning the signalment, geographic distribution, seasonal onset, treatment, and survival of affected dogs. Animals: Sixty Pugs with NME and 14 contemporaneous control Pugs with other intracranial diseases (non‐NME group). Methods: Pugs that were euthanized or died because of intracranial disease were prospectively obtained. All dogs had necropsy, histopathology, and testing for various infectious diseases and were subsequently divided into NME and non‐NME groups. Signalment, geographic distribution, seasonal onset, treatment, and survival were compared between groups. Results: In Pugs with NME, median age at onset of clinical signs was 18 months (range, 4–113 months). A greater proportion of female dogs were present in the NME group (40/60) compared with the control group (6/14). Pugs with NME had a significantly lower mean weight (7.81 kg) than control Pugs (9.79 kg) (P= .012). Mean survival in Pugs with NME was 93 days (range, 1–680 days), with dogs receiving any form of treatment living significantly longer than those that were not treated (P= .003). Anticonvulsive drugs were the only treatment significantly associated with longer survival (P= .003). Conclusions and Clinical Importance: NME appears to be a common cause of intracranial signs in Pugs, based on the high proportion of NME dogs reported in this population. Pugs with NME are most commonly young adult female dogs. Although further investigation is needed to determine the optimal treatment of NME, anticonvulsive drugs appear to beneficially affect duration of survival.

A case report of hepatocellular carcinoma and focal nodular hyperplasia with a myelolipoma in two chimpanzees and a review of spontaneous hepatobiliary tumors in non-human primates

Abstract:  Spontaneous hepatobiliary tumors in non‐human primates are uncommon. Here we report a case of hepatic carcinoma and a case of hepatic focal nodular hyperplasia (FNH) and myelolipoma in two captive chimpanzees. A 16‐year‐old male chimpanzee (4X0392) died after an 8‐month history of hepatic amyloidosis and low‐grade anemia. Necropsy findings included a hepatic neoplasm with highly pleomorphic hepatocytes arranged into irregular thickened trabeculae. The diagnosis was high‐grade hepatocellular carcinoma. A second male chimpanzee (4X0080), 23 years of age, died suddenly of heart failure secondary to cardiomyopathy. An incidental finding at necropsy was a liver mass characterized by multinodularity, prominent fibrous septa, and biliary hyperplasia. These features were consistent with FNH. While 4X0392 had no history of experimental viral exposure, 4X0080 was vaccinated with inactivated hepatitis B virus, an attenuated hepatitis A virus, and was experimentally infected with hepatitis C virus and human immunodeficiency virus. A survey of the literature revealed 68 reported cases of hepatobiliary tumors in non‐human primates, including 12 hepatocellular adenomas, eight cholangiocellular adenomas/cystadenomas, 22 hepatocellular carcinomas, seven cholangiocarcinomas, and seven gallbladder adenocarcinomas. The majority of reported cases have been in prosimians and Old World monkeys. Hepatic neoplasia is rare in chimpanzees. Only four hepatic neoplasms have been reported in chimpanzees, three of which were associated with viral hepatitis. FNH has not been previously described in any non‐human primate.

Eight Cases of Feline Cutaneous Leishmaniasis in Texas

Leishmaniasis is a zoonotic disease caused by intracellular Leishmania protozoa that are transmitted by sandflies. The disease occurs in 3 forms: cutaneous, mucocutaneous, and visceral. Cutaneous leishmaniasis has been reported in cats in Europe and South America and in 1 cat from Texas. Leishmania mexicana is endemic in Texas and has been reported to cause cutaneous lesions in humans. This article describes the pathology of 8 biopsy cases of feline cutaneous leishmaniasis presented to the Texas Veterinary Medical Diagnostic Laboratory over a 3.5-year period. The median age of the cats was 3 years; each was presented with nodular, ulcerative lesions on the pinnae and less commonly on the muzzle and periorbital skin. Histologically, the lesions were nodular to diffuse histiocytic dermatitis with numerous amastigotes (2–4 μm) within macrophages and occasionally within the interstitium. Organisms were often contained within round, clear, intracellular vacuoles. In areas of necrosis, organisms were also free within the interstitium. The overlying epidermis was hyperkeratotic, hyperplastic, and often ulcerated. The organisms were not argyrophilic (Gomori methenamine silver), reacted poorly with periodic acid–Schiff reagent, and were inconsistently basophilic with Giemsa. Although not readily visible histologically, kinetoplasts were evident in amastigotes in cytologic preparations. The lesions were similar to those described for cutaneous L. mexicana infection in humans. In 5 of the 8 cats, Leishmania mexicana DNA was amplified from paraffin-embedded tissue by polymerase chain reaction and sequenced.

Polyarteritis nodosa in a cynomolgus macaque (Macaca fascicularis).

Polyarteritis nodosa (PAN) is an idiopathic necrotizing vasculitis affecting small- to medium-sized arteries. The disease is well recognized in humans, and PAN-like syndromes have been described in a number of other species. This report describes a case of PAN in a 6-year-old male cynomolgus macaque. The animal had necrotizing arteritis affecting vessels in the kidney, small intestine, colon, heart, spleen, mesentery, urinary bladder, and pancreas. The lesions were segmental in distribution and of varying severity and stage of development. A transmural mixed inflammatory cell infiltrate was present, often accompanied by fibrinoid necrosis of the tunica media and loss of the internal elastic lamina. Immunohistochemical staining showed that many of the infiltrating cells were T lymphocytes and histiocytes, suggesting a cell-mediated component to the pathogenesis.

Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius

ABSTRACT A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease. IMPORTANCE Ball pythons are popular pets because of their diverse coloration, generally nonaggressive behavior, and relatively small size. Since the 1990s, veterinarians have been aware of an infectious respiratory disease of unknown cause in ball pythons that can be fatal. We used unbiased shotgun sequencing to discover a novel virus in the order Nidovirales that was present in cases but not controls. While nidoviruses are known to infect a variety of animals, this is the first report of a nidovirus recovered from any reptile. This report will enable diagnostics that will assist in determining the role of this virus in the causation of disease, which would allow control of the disease in zoos and private collections. Given its evolutionary divergence from known nidoviruses and its unique host, the study of reptile nidoviruses may further our understanding of related diseases and the viruses that cause them in humans and other animals. Ball pythons are popular pets because of their diverse coloration, generally nonaggressive behavior, and relatively small size. Since the 1990s, veterinarians have been aware of an infectious respiratory disease of unknown cause in ball pythons that can be fatal. We used unbiased shotgun sequencing to discover a novel virus in the order Nidovirales that was present in cases but not controls. While nidoviruses are known to infect a variety of animals, this is the first report of a nidovirus recovered from any reptile. This report will enable diagnostics that will assist in determining the role of this virus in the causation of disease, which would allow control of the disease in zoos and private collections. Given its evolutionary divergence from known nidoviruses and its unique host, the study of reptile nidoviruses may further our understanding of related diseases and the viruses that cause them in humans and other animals.

Tay-Sachs disease in Jacob sheep

Autopsy studies of four Jacob sheep dying within their first 6-8 months of a progressive neurodegenerative disorder suggested the presence of a neuronal storage disease. Lysosomal enzyme studies of brain and liver from an affected animal revealed diminished activity of hexosaminidase A (Hex A) measured with an artificial substrate specific for this component of β-hexosaminidase. Absence of Hex A activity was confirmed by cellulose acetate electrophoresis. Brain lipid analyses demonstrated the presence of increased concentrations of G(M2)-ganglioside and asialo-G(M2)-ganglioside. The hexa cDNA of Jacob sheep was cloned and sequenced revealing an identical number of nucleotides and exons as in human HexA and 86% homology in nucleotide sequence. A missense mutation was found in the hexa cDNA of the affected sheep caused by a single nucleotide change at the end of exon 11 resulting in skipping of exon 11. Transfection of normal sheep hexa cDNA into COS1 cells and human Hex A-deficient cells led to expression of Hex S but no increase in Hex A indicating absence of cross-species dimerization of sheep Hex α-subunit with human Hex β-subunits. Using restriction site analysis, the heterozygote frequency of this mutation in Jacob sheep was determined in three geographically separate flocks to average 14%. This large naturally occurring animal model of Tay-Sachs disease is the first to offer promise as a means for trials of gene therapy applicable to human infants.

Heritability and transmission analysis of necrotizing meningoencephalitis in the Pug

Necrotizing meningoencephalitis (NME) in the Pug is an invariably fatal disease with an early age of onset whose cause remains unknown. Breed predilection strongly suggests genetic component(s), and viral etiology proves negative in studied cases. The current study was undertaken as the first analysis of the heritable component(s) involved in NME in the Pug. Complete medical records, individual characteristics, and pedigree information were collected for 58 affected dogs with data pertaining to 4698 dogs analyzed. A high inbreeding coefficient with differences across gender and significant differences across coat color classes and variable expression was evident. Median onset age was 19months and median survival time 23days. Screening for herpes-, adeno-, and parvoviruses was negative. The data demonstrate a strong familial inheritance of NME in the Pug. This investigation provides parameters of disease from the largest Pug NME cohort analyzed to date and offers evidence of previously unrecognized familial inheritance.