Red neurons in ovine polioencephalomalacia (cerebrocortical necrosis) are strongly amyloid precursor protein immunopositive.

The signature pathological feature of the pseudolaminar cerebrocortical necrosis found in polioencephalomalacia (PEM) of ruminants is the development of red (eosinophilic) neurons. These neurons are generally considered to be irredeemably injured but we have shown, for the first time, in ovine PEM cases, that most strongly express amyloid precursor protein (APP), which has a neuroprotective role in the brain. By contrast, neurons in unaffected cerebral cortices from control sheep were APP immunonegative. This finding suggests that, rather than being inevitably destined to die, some of these APP immunoreactive cortical neurons may survive and regain structural and functional integrity.

Heterogeneous immunoreactivity of axonal spheroids in focal symmetrical encephalomalacia produced by Clostridium perfringens type D epsilon toxin in sheep.

Since axonal injury (AI) is an important component of many veterinary neurologic disorders, we assessed the relative ability of a panel of antibodies (amyloid precursor protein, 3 subunits of neurofilament protein, protein gene product 9.5, ubiquitin, and synaptophysin) to detect axonal swellings or spheroids. Abundant axonal spheroids found in necrotic internal capsule foci produced in 4 sheep by chronic Clostridium perfringens type D epsilon neurotoxicity provided a model system in which to evaluate this important diagnostic tool. There was heterogeneous labeling of subsets of spheroids by the respective antibodies, suggesting that, in order to detect the complete spectrum of AI in diagnostic cases, a range of antibodies should be used, not only when spheroids are plentiful but also when they are few in number or incompletely developed. The application of insufficient markers in the latter cases can potentially lead to the contribution of AI to lesion pathogenesis being underappreciated.

Striatal necrosis caused by Lichtheimia ramosa in a neonatal calf.

A 12-day-old male calf that did not want breast milk from birth died following neurological signs such as staggering. Postmortem examination revealed bleeding and encephalomalacia in the left striatum and frontal lobe. Histopathologically, necrotic granulomatous encephalitis with numerous fungi was detected. The fungi were positively stained with anti-Rhizomucor mouse monoclonal antibodies. Lichtheimia ramosa was detected in formalin-fixed paraffin-embedded samples of the affected tissue by molecular methods. To the best of our knowledge, striatal necrosis caused by L. ramosa in a neonatal calf has not been reported. This study provides the first evidence of striatal necrosis caused by L. ramosa in a neonatal calf.

Biofuels Co-Products Tolerance and Toxicology for Ruminants: An Update.

Corn co-products are a co-product of the dry and wet corn-milling ethanol manufacturing industry. The dry mill corn co-product is distiller's grains. Distillers grain can be further categorized into dry distillers grains (DDG), DDG with solubles, wet distillers grains with solubles (WDGS), modified WDGS, and corn syrup (solubles). Wet mill ethanol production produces 2 main feed stuffs: corn gluten (wet and dry) and heavy steep water.

Diabetes Mellitus With Concurrent Cerebellar Degeneration and Necrosis in a Domestic Goose ( Anser anser domesticus).

A 5-year-old sexually intact male Toulouse goose ( Anser anser domesticus) was presented for ataxia, polyuria, and polydipsia. The goose was cachectic and exhibited head tremors. Results of plasma biochemical analysis and point-of-care glucometry revealed persistent hyperglycemia. Despite supportive care and oral glipizide, the goose died within 48 hours of presentation. Necropsy revealed severe pancreatic atrophy and fibrosis with regionally extensive cerebellar encephalomalacia and generalized Purkinje cell degeneration and necrosis. On a wet basis, hepatic zinc concentration was determined to be twice the reference interval by atomic absorption spectroscopy. Based on these findings, the pancreatic insufficiency with secondary diabetes mellitus was attributed to chronic zinc toxicosis. Despite birds' relative resistance to high blood glucose concentrations, prolonged hyperglycemia is suspected to have caused selective Purkinje cell degeneration and necrosis by glial activation, mitochondrial dysfunction, and glutamate toxicity, which resulted in the clinically observed motor deficits. This is consistent with experimental diabetic rat models. This case highlights the need for further investigation of the complex pathophysiology of diabetes mellitus in birds.

Histopathological study of encephalomalacia in neonatal calves and application of neuronal and axonal degeneration marker.

Five calves that had shown neurological symptoms within 9 days after birth were histopathologically diagnosed as encephalomalacia. Two calves showed bilateral laminar cerebrocortical necrosis and neuronal necrosis in the corpus striatum and hippocampus. Since the distributional pattern of the lesions was consistent with that of global ischemia in other species, the lesions were probably hypoxic/ischemic encephalopathy consistent with the history of dystocia and perinatal asphyxia. One calf also showed bilateral laminar cerebrocortical necrosis. However, the lesions were chronic ones, because the calf had survived for long time and necropsied at postnatal day 118. Additionally, the lesions did not involve the corpus striatum and hippocampus. The other two calves showed multifocal necrosis with vascular lesions characterized by fibrin thrombi, perivascular edema and perivascular hyaline droplets in the cerebral cortex, corpus striatum, thalamus, brain stem and cerebellum. Considering the age of onsets and histopathological appearance, it was possible that latter three calves were also hypoxic/ischemic encephalopathy, however, exact cause of them was not revealed. In all calves, degenerated/necrotic neurons showed positive reactions for Fluoro-Jade C and degenerated axons showed immunoreactivity for Alzheimer precursor protein A4. Therefore, these markers were applicable to examination of brain injury in neonatal calves.

Cerebral Disorders of Calves.

Neurologic diseases of the cerebrum are relatively common in cattle. In calves, the primary cerebral disorders are polioencephalomalacia, meningitis, and sodium toxicity. Because diagnostic testing is not always readily available, the practitioner must often decide on a course of treatment based on knowledge of the likely disease, as well as his or her own clinical experience. This is particularly true with neurologic diseases in which the prognosis is often poor and euthanasia may be the most humane outcome. This article reviews the most common diseases affecting the cerebrum of calves with a focus on pathophysiology, diagnosis, and treatment.

Polioencephalomalacia and Heart Failure Secondary to Presumptive Thiamine Deficiency, Hepatic Lipidosis, and Starvation in 2 Abandoned Siamese Cats.

Two 4-year-old spayed female Siamese cats were seized by the British Columbia Society for the Prevention of Cruelty to Animals after confinement to an abandoned housing unit without food for 9 weeks. One cat was found dead, and the second was euthanized within 24 hours due to neurologic deterioration despite therapy. Polioencephalomalacia of the caudal colliculus, hepatic lipidosis, cachexia, and congestive heart failure with cardiomyocyte atrophy were identified in both cats through postmortem examination and attributed to a prolonged period of starvation. Brain lesions were likely the result of thiamine deficiency (Chastek paralysis), which can be associated with both malnutrition and liver disease. This case highlights the importance of thiamine supplementation during realimentation of cats with hepatic lipidosis. Heart failure resulting from cachexia may have contributed to the death of the first cat and the morbidity of the second cat.

Toxicology for the Equine Practitioner.

A wide variety of toxins cause diseases in the horse and are investigated routinely by veterinarians and veterinary pathologists to identify the cause of illness and death. A complete investigation involves performing a thorough necropsy and requires macroscopic and microscopic examination of lesions and a variety of laboratory testing to obtain an accurate diagnosis. The identification of gross lesions by equine practitioners is often the first step in formulating a diagnostic plan. This article provides a description of selected common toxins producing detectable gross lesions in horses in North America. The article is useful to equine practitioners and veterinary pathologists investigating a toxicology-related death.

Consideration of evidence for therapeutic interventions in bovine polioencephalomalacia.

Randomized, masked, prospective clinical trial evidence for therapeutic intervention in naturally occurring bovine polioencephalomalacia (polio) is nonexistent. This article evaluates the use of thiamine and anti-inflammatories in the therapy of polioencephalomalacia based on available information related to the pathophysiology of the disease, induced models, disease outcome in other species (sheep), and parallels in similar disease in humans.

Surto de intoxicação por sal em ovinos no estado do Pará / Salt poisoning outbreak in sheep in the state of Pará

O presente trabalho relata um surto de intoxicação por sal em ovinos no Brasil, em uma propriedade no estado do Pará. De um total de 545 ovinos, oito animais adoeceram (1,46%) e quatro destes morreram (50%). A avaliação das instalações e do manejo indicaram como fatores predisponentes a ingestão excessiva de mistura mineral e a restrição hídrica. Os principais sinais clínicos foram decúbito, diminuição ou ausência da sensibilidade cutânea, ausência dos reflexos de ameaça, palpebral e auricular, midríase, nistagmo, opistótono, espasticidade de membros, sonolência e estupor. Havia ainda, timpanismo, diarreia, taquipneia, taquicardia, desidratação e poliúria. A evolução do quadro clínico nos animais que morreram variou de duas horas e meia a 48 horas. As médias das concentrações séricas de sódio e de potássio de 31 ovinos do mesmo lote afetado pela intoxicação, em amostras colhidas durante o surto, revelaram hipernatremia (190mEq/l) e hipercalemia (8,2mEq/l). À necropsia, observou-se em um animal, achatamento das circunvoluções cerebrais. Microscopicamente, neste animal, evidenciou-se vacuolização moderada do neurópilo, particularmente nas lâminas intermediárias do córtex cerebral, com aumento dos espaços perineural e perivascular. Nessas áreas foram observados ainda, acentuada tumefação e edema dos astrócitos e necrose neuronal aguda. A dosagem de sódio no encéfalo de um ovino, revelou-se elevada com valor de 3.513ppm. O diagnóstico foi realizado com base na epidemiologia, nos sinais clínicos, nas lesões macro e microscópicas e nas dosagens de sódio no soro e no encéfalo dos ovinos.(AU)

This paper reports an outbreak of salt poisoning in sheep on a farm in the state of Pará, northern Brazil. Eight (1.46%) animals were affected from a total of 545 sheep and four (50%) of them died. The evaluation of the facilities and the handling indicated as predisposing factors excessive intake of the mineral supplement and water restriction. The main clinical signs were recumbency, decrease or absence of cutaneous sensibility, absence of auricular, palpebral and menace reflex, mydriasis, nystagmus, opisthotonus, spasticity of limbs, somnolence and stupor. Beside these signs bloat, diarrhea, tachypnea, tachycardia, dehydration and polyuria were observed. The course of the disease in animals that died ranged from two hours and a half to 48 hours. The medium of serum concentration of sodium and potassium of 31 sheep from the same group affected on samples collected during the outbreak revealed hypernatremia (190mEq/l) and hyperkalemia (8.2mEq/l). At necropsy, there was flattening of the cerebral gyri in one sheep; in this animal was found vacuolization of the neuropil in the cerebral cortex with moderate intensity in the intermediary and mild on the superficial layers, with increased perineural and perivascular spaces. In these areas there were markedly swollen nucleus of astrocytes with acute neuronal necrosis. The dosage of sodium in the brain of a sheep revealed a high value of 3.513ppm. The diagnosis was made based on the epidemiology, clinical signs, macro and microscopic lesions and in the dosages of sodium in serum and brain.(AU)

Bovine diseases causing neurological signs and death in Mexican feedlots.

The number of large feedlot operations, similar to that of USA and Canada, has notably increased in Mexico in the last three decades. Clinical and laboratory diagnoses of neurological diseases in feedlot cattle are crucial in Mexico and Central America because of the high incidence of bovine paralytic rabies (BPR). Because of its zoonotic potential, BPR must be promptly diagnosed and differentiated from other bovine neurological diseases such as thrombotic meningoencephalitis (TME), polioencephalomalacia (PEM) and botulism. More recently, BPR and botulism have been diagnosed with increasing frequency in Mexican feedlots. Neither BPR nor botulism has relevant gross lesions, thus post-mortem diagnosis without laboratory support is impossible. Herein, we describe five outbreaks of neurological diseases in Mexican feedlots in which BPR, botulism and PEM were diagnosed either independently or in combination. A diagram illustrating the most conspicuous pathologic findings and ancillary laboratory test required to confirm the diagnoses of these neurological diseases in feedlot cattle is proposed.

Polioencephalomalacia secondary to hypernatremia in squirrel monkeys (Saimiri sciureus).

Squirrel monkeys (Saimiri spp) are one of the most consistently used New World primates in biomedical research and are increasingly being used in neuroscience research, including models of drug abuse and addiction. Spontaneous neurologic disease in the squirrel monkey is uncommonly reported but includes various infectious diseases as well as cerebral amyloidosis. Hypernatremia is an extremely serious condition of hyperosmolarity that occurs as a result of water loss, adipsia, or excess sodium intake. Neurologic effects of hypernatremia reflect the cellular dehydration produced by the shift of water from the intracellular fluid space into the hypertonic extracellular fluid space. Severe hypernatremia may result in cerebrocortical laminar necrosis (polioencephalomalacia) in human patients as well as in a number of domestic species, including pigs, poultry, and ruminants. We report the clinical, histopathologic, and immunohistochemical findings of polioencephalomalacia in 13 squirrel monkeys. Polioencephalomalacia in these animals was associated with hypernatremia that was confirmed by serum levels of sodium greater than 180 mmol/L (reference range, 134.0-154.0 mmol/L [mEq/L]). All animals had concurrent diseases or experimental manipulation that predisposed to adipsia. Immunohistochemical investigation using antibodies to neuronal nuclei (NeuN), CNPase, Iba-1, and CD31 revealed necrosis of predominantly cerebral cortical layers 3, 4, and 5 characterized by neuronal degeneration and loss, oligodendrocytic loss, microglial proliferation, and vascular reactivity. The squirrel monkey is exquisitely sensitive to hyperosmolar metabolic disruption and it is associated with laminar cortical necrosis.

Understanding the role of sulfur-thiamine interaction in the pathogenesis of sulfur-induced polioencephalomalacia in beef cattle.

This study examined the role of sulfur (S) in the pathogenesis of S-induced polioencephalomalacia (PEM) in beef cattle in the context of thiamine status and metabolism. Thiamine, thiamine monophosphate (TMP) and thiamine pyrophosphate (TPP) status in rumen fluid, blood and brain tissue were determined in beef heifers fed 2 levels of S [low S (LS) vs. high S (HS)] at 2 forage-to-concentrate ratios (F:C). High S diet did not affect ruminal and blood thiamine status. Interestingly, however, HS diet showed increased brain thiamine levels. No gross or histopathological changes indicative of PEM were detected in the brains of the heifers. Of note, during the course of the present study, we documented an outbreak of S-induced PEM in commercial feedlot steers. Brain thiamine variables in experimental animals fed HS diet were then contrasted with brain thiamine status in PEM affected feedlot steers. Interestingly, in clinically normal animals, exposure to HS diet resulted in increased levels of both TMP and TPP in the brain tissue, in comparison to animals fed LS diet. In contrast, the PEM affected brains showed overall lower levels of thiamine phosphates. It is noteworthy that TPP levels were 36.5% lower, despite 4.9-fold higher free thiamine in PEM brains compared to normal brains. Our results indicate that high dietary S may increase the metabolic demand for TPP, and that animals incapable of maintaining requisite levels of brain TPP are at high risk to develop fulminant cerebrocortical necrosis.