Enteric dysganglionosis resembling intestinal neuronal dysplasia in a foal with bacterial colitis.

A 5-day-old quarter horse colt with a history of hypothermia, agonal breathing, and diarrhea was euthanized. At necropsy, numerous slightly raised, discrete, closely approximated submucosal nodules were observed in the colon and small intestine. Histologically, these nodules were composed of expanded submucosal mesenchyme that contained numerous neurons either individually or in ganglia. Thirty-two percent of these ganglia included 8 or more neurons, in contrast to 6% in an age-matched foal. Some nodules had necrosuppurative inflammation with vasculitis, thrombosis, and bacterial colonization. A few heterotopic neurons were randomly distributed in the mucosa and the muscularis mucosa. Histologic changes were most consistent with intestinal neuronal dysplasia, a disease of the submucosal plexus described in humans.

Hypoxic/ischemic encephalopathy associated with placental insufficiency in a cloned foal.

Hypoxic/ischemic encephalopathy in a cloned American Quarter horse foal was initially associated with placental insufficiency and exacerbated by protracted hypotension during anesthesia for a surgical procedure. The foal, born at the Texas A&M Veterinary Medical Center, was diagnosed at birth with neonatal maladjustment syndrome that was accompanied by dysmaturity, muscle contracture of the front limbs, and a blood clot within the lumen of the urinary bladder. Seizures that developed after anesthesia were attributed to hypoxia/ischemia during anesthesia and culminated in death. Macroscopically, the cerebrum had flattened cerebral gyri with shallow sulci, yellowish cortical discoloration, and apple-green autofluorescence (under 365-nm ultraviolet light) at the cortical/white matter junction. Microscopically, there was laminar cortical necrosis with prominent diffuse ischemic change of neuronal cell bodies. The white matter had prominent rarefaction with focal axonal and myelin degeneration and focal macrophage (gitter cell) accumulation. Additionally, there was astrocytic hypertrophy with gemistocyte formation. The chorioallantois was diffusely thickened in the area corresponding to the uterine horns. Histologically, microcotyledons were markedly attenuated with absence of chorionic villi.

Colonic ganglioneuromatosis in a horse.

Ganglioneuromas are complex tumors that arise in peripheral ganglia and are composed of well-differentiated neurons, nerve processes, Schwann cells, and enteric glial cells. The term ganglioneuromatosis (GN) denotes a regional or segmental proliferation of ganglioneuromatous tissue. This report describes an 8-year-old mixed breed horse with GN in a 25-cm segment of small colon. Grossly, the lesion consisted of numerous sessile to pedunculated nodules extending from the serosal surface. Histologic examination revealed the nodules to consist of fascicles of spindle-shaped cells consistent with Schwann cells, clusters of neurons, supporting enteric glial cells, and thick bands of perineurial collagen. Most of the nodules coincided with the location of the myenteric plexus and extended through the outer layer of the tunica muscularis to the serosal surface. Neuronal processes were demonstrated within the lesion with electron microscopy. With immunohistochemistry neurons were positive for neuron specific enolase (NSE) and S-100 and the Schwann cells and enteric glial cells were positive for S-100 and glial fibrillary acidic protein (GFAP). The pathogenesis of GN is poorly understood. GN, although rare, should be included in the differential diagnosis of gastrointestinal tumors in the horse.

Immunohistochemical evaluation of mx protein expression in canine encephalitides.

Mx proteins are a group of interferon-induced GTPases whose expression has been demonstrated in a number of human viral infections and in some idiopathic inflammatory diseases. In this study, the expression of Mx protein was evaluated in known viral, nonviral, and idiopathic encephalitides in the dog via immunohistochemistry using an antibody against human MxA. All 12 cases of confirmed viral encephalitis, including 7 cases of canine distemper, 4 cases of canine herpesvirus, and 1 case of rabies, were Mx positive. In canine distemper cases, staining was particularly strong and a variety of cell types were positive, including astrocytes, macrophages/microglia, and neurons. Immunoreactivity for Mx protein was evident in a few cases of nonviral infectious encephalitis, including neosporosis (1/1), Chagas disease (2/3), aspergillosis (1/2), and encephalitozoonosis (1/1). Consistent staining was observed in most cases of idiopathic encephalitis, including granulomatous meningoencephalomyelitis (7/7), necrotizing meningoencephalitis of pug dogs (6/7), and necrotizing encephalitis of the Yorkshire Terrier (3/3) and Maltese (1/1) breeds. Mx staining was negative in 5 normal dog brains; 3 cases of cryptococcosis; and single cases of blastomycosis, protothecosis, and bacterial meningitis.

Primitive neuroectodermal tumor in the spinal cord of a brahman crossbred calf.

A variety of embryonal tumors of the central nervous system, typically malignant and occurring in young individuals, are recognized in humans and animals. This report describes an invasive subdural but predominantly extramedullary primitive neuroectodermal tumor developing at the lumbosacral junction in a 6-month-old Brahman crossbred calf. The tumor was composed of spindloid embryonal cells organized in interlacing fascicles. The cells had oval to elongate or round hyperchromic nuclei, single to double nucleoli, and scant discernible cytoplasm. Immunohistochemical staining for neuron-specific enolase, synaptophysin, and S-100 protein and formation of pseudorosettes suggested neuronal and possibly ependymal differentiation.

Natural bovine lentivirus type 1 infection in Holstein dairy cattle. II. Lymphoid tissue lesions.

Bovine immunodeficiency virus (BIV) in Holstein cows was associated with morphologic evidence of lymphoid organ deficiency. Cows were subjected to normal management practices including parturition and lactation without adverse environmental stresses. During the clinical disease process there was marked weight loss and wasting with frequent and severe concurrent infections. Lymphoid follicular hyperplasia and dysplasia in lymph nodes, and hypertrophy and hyperplasia in hemal lymph nodes were characteristics of the lymphoid tissues. Atrophy of lymphoid cell compartments with depletion of lymphocytes and a lymphocytic lymphoid folliculitis were components of the lymphoid system pathology. The nodal tissue lesions resembled those observed in feline, simian, and human lentiviral disease. A functional correlation with immune system deficiency was the development of multiple bacterial infections which failed to resolve after appropriate therapy. The BIV-associated disease syndrome in dairy cows may be useful as a model system for investigation of the pathogenesis of the lymphoid organ changes that occur in humans and animals with lentiviral infection.

Natural bovine lentiviral type 1 infection in Holstein dairy cattle. I. Clinical, serological, and pathological observations.

Clinical, serological, and pathological abnormalities observed in Holstein cows naturally infected with bovine lentivirus 1 bovine immunodeficiency virus (BIV) and other infections were progressive and most commonly associated with weight loss, lymphoid system deficiency, and behavioral changes. Clinical evidence of meningoencephalitis was dullness, stupor, and occasional head or nose pressing postures. The polymerase chain reactions associated the BIV provirus with the lesions in the central nervous system and lymphoid tissues. Multiple concurrent infections developed in retrovirally infected cows undergoing normal stresses associated with parturition and lactation. A major functional correlate of the lymphoreticular alterations was the development of multiple secondary infections which failed to resolve after appropriate antibacterial therapy. The chronic disease syndrome in dairy cows associated with BIV may be useful as a model system for investigation of the pathogenesis of the nervous system lesions and lymphoid organ changes that occur in humans with lentiviral infection.

Immunohistochemical staining patterns of canine meningiomas and correlation with published immunophenotypes.

This study examined immunohistochemical staining patterns for several meningioma variants involving either the brain or spinal cord of dogs. Formalin-fixed, paraffin-embedded tissue from 15 tumors was obtained. The selected tumor group included seven meningothelial, three transitional, two malignant (anaplastic), one myxoid, one papillary, and one osteomatous meningiomas. Tumors were evaluated for reactivity to the following six immunohistochemical markers: vimentin, pancytokeratin, glial fibrillary acidic protein (GFAP), S100, neuron-specific enolase (NSE), and synaptophysin. Vimentin expression was detected in all meningiomas, and 14 of 15 tumors demonstrated intense vimentin staining in more than 50% of the neoplastic cells. Pancytokeratin expression was present in 11 of 15 neoplasms; however, positive staining frequently was focal and often involved a small percentage of the neoplastic cells. GFAP expression was detected in a single, anaplastic meningioma. Although expression of NSE and S100 was detected in 12 of 25 meningiomas, the intensity of the staining and the percentage of positive neoplastic cells was highly variable. Synaptophysin was uniformly negative. These results will help to establish immunohistochemical profiles for meningiomas that will improve our ability to correctly differentiate these neoplasms of meningeal origin from central nervous system tumors originating from other sites.

Symptomatic granular cell tumor involving the pituitary gland in a dog: a case report and review of the literature.

A granular cell tumor involving the pituitary gland, optic chiasm and ventral pyriform lobes was discovered in a 12-year-old Labrador Retriever. Clinical signs included acute blindness, seizures, ataxia, weakness, and behavioral changes. The diagnosis was established by histopathologic and ultrastructural examination of neoplastic tissues collected at necropsy. Granular cell tumors involving the central nervous system are well documented in humans but rarely have been described in dogs. The location of the neoplasm and the clinical symptoms seen in this dog closely parallel those of a rare syndrome in humans commonly described as symptomatic parasellar or pituitary granular cell tumors. The cell of origin for these tumors is still highly debated, and attempts to characterize human granular cell tumors through immunohistochemistry have produced conflicting results. An immunohistochemical profile of this neoplasm revealed focal positive staining for vimentin with a lack of staining for neuron-specific enolase, glial fibrillary acidic protein, S-100, and synaptophysin. All neoplastic cells were strongly positive with the periodic acid-Schiff reaction.

Thrombosis of the caudal vena cava presenting as an unusual cause of an abdominal mass and thrombocytopenia in a dog.

Thrombosis of the caudal vena cava in a dog secondary to metastatic neoplasia is described. The dog had a palpable abdominal mass and persistent thrombocytopenia due to a thrombosed caudal vena cava that was surgically removed. A few days after its removal, the dog died and neoplastic cells of neural crest origin were identified at the edge of the thrombus. Massive thrombosis can be an unusual cause of platelet consumption, leading to thrombocytopenia and disseminated intravascular coagulation. Deep vein thrombosis of the vena cava can occur in dogs and may mimic an abdominal mass. Multiple mechanisms may be involved in the development of venous thrombosis, including endothelial damage by neoplastic cells and the presence of a hypercoagulable state secondary to neoplasia. Extensive collateral circulation may allow removal of diseased vena cava.

Computed tomographic findings of ceroid lipofuscinosis in a dog.

A two-year and seven-month-old, castrated male border collie was presented for a two-month history of progressive neurological signs including blindness, ataxia, dementia, and partial seizures. A complete blood count, serum biochemical profile, urinalysis, thoracic radiographs, and cerebrospinal fluid analysis were within reference ranges. Computed tomography (CT) of the brain showed dilatation of the ventricles and atrophy of the cerebral cortex. A central nervous system (CNS) storage disease was suspected, and the dog was euthanized due to a poor prognosis. Light and electron microscopic examination revealed neuronal degeneration with pigment accumulation in neurons of the CNS, in ganglia of the peripheral nervous system, and in several non-nervous tissues. Ceroid lipofuscinosis was diagnosed based on the microscopic and ultrastructural lesions detected. This is the second report of CT findings in a canine clinical patient with ceroid lipofuscinosis.

Rectal stricture in an ostrich (Struthio camelus).

Exploratory celiotomy of an 18-mo-old female ostrich (Struthio camelus) with anorexia, lethargy, and constipation of 5 days' duration showed mesenteric volvulus and a focal narrowing of the rectum approximately 28 cm cranial to the cloaca. The prognosis was poor and the animal was euthanized. Necropsy revealed a fibrinonecrotic proctitis and a 3-cm-long circumferential stricture of the rectum. Histologically, the rectal wall at the stricture was deeply effaced by fibrovascular connective tissue with vascular thrombosis and necrotizing vasculitis, and it resembled the lesions in feeder pigs with fibrinonecrotic colitis.

Natural and experimental bovine immunodeficiency virus infection in cattle.

Since 1989, the LSU dairy herd, with its high seroprevalence of BIV, was recognized to have a high incidence of common diseases that reduced the economic viability of the dairy. The herd had a high percentage of cows with encephalitis associated with depression and stupor, alteration of the immune system associated with secondary bacterial infections, and chronic inflammatory lesions of the feet and legs. The occurrence of disease problems was associated with the stresses of parturition and early lactation and/or with unusual environmental stress cofactors.

Neuronal ceroid lipofuscinosis in Rambouillet sheep: characterization of the clinical disease.

A chronic progressive, neurodegenerative disease has been identified in 4 closely related flocks of purebred Rambouillet sheep. Blindness, circling, proprioceptive deficits, reduced cognition, and poor body condition are the main clinical signs. Prominent lesions include markedly decreased cerebral size and weight, enlarged cerebral ventricles, and intraneuronal accumulations of autofluorescent pigment. Affected sheep usually die between 1 and 2 years of age. The clinical signs and postmortem findings are consistent with neuronal ceroid-lipofuscinosis.

Juvenile-onset neuronal ceroid-lipofuscinosis in Rambouillet sheep.

Two, 8-month-old Rambouillet half-sister ewes with signs of visual loss and decreased mentation were examined. Ewe No. 1 was necropsied at 10 months of age, and after being held under observation for a further 6 months, ewe No. 2 was necropsied at 16 months of age. At that time, the ewe was blind and severely depressed. Both ewes had deposition of an autofluorescent lipopigment, identified as ceroid-lipofuscin, in neurons of the brain, spinal cord, eye, and dorsal root ganglia. The disease process was progressive and characterized by deposition of lipopigment with neuronal degeneration and severe fibrillary astrogliosis. This progressive loss of neurons in the older ewe led to severe retinal degeneration. No pigment was observed in cells outside of the nervous system and eye. Controlled breeding studies have shown that this disease has an autosomal, recessive inheritance. The disease referred to here as juvenile-onset neuronal ceroid-lipofuscinosis of Rambouillet sheep is unlike the majority of the hereditary ceroid-lipofuscinoses that occur in human beings and animals in that only the nervous system is affected. Therefore, this disease could serve as an excellent model for the study of lipopigment deposition that affects the nervous system as a result of various disease states and during aging.

Neuronal vacuolization and necrosis induced by the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK(+)801 (dizocilpine maleate): a light and electron microscopic evaluation of the rat retrosplenial cortex.

MK(+)801 (dizocilpine maleate) is a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor, the major glutamate receptor at excitatory synapses in the central nervous system. Since NMDA antagonists are neuroprotective, there is interest in their development for treatment of cerebral ischemia. Unfortunately, many of these compounds also induce vacuole formation in neurons of the rat retrosplenial cortex (Olney et al., Science 244: 1360-1362, 1989). Although vacuolization was initially reported to be reversible with MK(+)801, preliminary data later suggested that higher doses might produce neuronal necrosis. To explore this issue, young male Sprague-Dawley rats were given a single subcutaneous dose of vehicle or 1, 5, or 10 mg/kg MK(+)801. At 4 h and 1, 2, 3, 4, 7, and 14 days postdose (DPD), the retrosplenial cortex was examined by light and electron microscopy. At 4 h, vacuoles occurred in neurons of retrosplenial cortical layers 3 and 4 in all rats given MK(+)801. Mitochondria and endoplasmic reticulum contributed to vacuole formation. At 1 DPD, vacuoles or necrotic neurons were rarely observed. At all subsequent time points, necrotic neurons were readily evident in rats given 5 or 10 mg/kg MK(+)801, but only rarely evident in rats given 1 mg/kg. Necrotic neurons were associated with reactive microglial cells that contained electron-dense debris ultrastructurally. If similar dose-dependent neuronal necrosis proves to be a feature of other NMDA antagonists, such effects might raise concerns for the development and use of these compounds in human cerebrovascular diseases.

Beta-mannosidosis in twelve Salers calves.

A diagnosis of beta-mannosidosis, a lysosomal storage disease caused by a deficiency of beta-mannosidase, was made in 12 purebred Salers calves. Affected neonatal calves were unable to rise and had intention tremors, hidebound skin, slightly domed calvaria, slight prognathism, and narrow palpebral fissures. Postmortem findings included variable dilatation of the lateral cerebral ventricles, marked pallor and paucity of white matter of the cerebrum and cerebellum, and mild to marked bilateral renomegaly. Microscopic lesions consisted of clear, intracytoplasmic vacuoles, which were especially prominent in neurons, thyroid follicular cells, proximal renal tubular epithelium, and reticuloendothelial cells. By ultrastructural examination, the intracytoplasmic vacuoles were identified as membrane-bound lysosomes distended by lucent material. The serum of affected calves was profoundly deficient in beta-mannosidase. Oligosaccharides, principally a trisaccharide with a terminal hexose in the beta-anomeric configuration, accumulated in tissues of affected calves. The percentage (37.2) of affected calves from groups of siblings, the approximately equal sex ratio, and the phenotypic normalcy of the parents of affected calves are compatible with an autosomal recessive mode of inheritance typical of other glycoproteinoses.