20-month-old, Charolais bull, Bos taurus.The bull presented to Veterinary Teaching Hospital with 7-day history of acute onset blindness. This patient is the most severely affected of 12 bulls exhibiting clinical signs (from total of 20). All bulls are housed on separate, but adjacent lots. The water source is pond and associated creek. The animals are fed 15-25lbs/head/day of a mixture of distillers grain, corn gluten, corn, soybean hulls and wheat ration with a small amount of hay (native grass). Some of the bulls were treated with thiamine, Nuflor, banamine and a multivitamin injection. There was no response to therapy. This patient was euthanized and submitted for necropsy to investigate cause of disease in herd.
Necropsy is performed on a 20 month-old (per history), white, 640 kg, Charolais bull in good body condition with no appreciable autolysis.Â Following comprehensive examination of the carcass and all major organ systems, there are no significant gross lesions (including the brain).Â
Histologic changes were confined to the cerebrum and overlying meninges.Â Within the deep cortical lamina, and segmentally, extending out to affect the more superficial laminae, the neuropil is moderately to markedly vacuolated and rarefied (necrosis) with infiltration of the neuropil by moderate to marked numbers of small glial cells, moderate numbers of gitter cells and fewer gemistocytic astrocytes.Â Cortical neurons are shrunken, angular, and hypereosinophilic with pyknotic nuclei (necrosis) and are often cuffed by glial cells (satellitosis).Â Vessels within the affected areas are lined by plump, hypertrophied endothelial cells and are frequently cuffed by large macrophages.Â The overlying meninges are infiltrated by low to moderate numbers of large, perivascular to diffusely distributed macrophages and mildly expanded by edema.Â
1.Â Cerebrum: Severe, subacute, locally extensive laminar cortical (neuronal) necrosis (polioencephalomalacia).
2.Â Meninges: Mild to moderate histiocytic meningitis.
Feed analysis, sulfur, 4200ppm
Water analysis, sulfates, <7mg/L
Blood lead, negative
Histologic lesions in the cerebrum of this bull were characteristic of nutritional polioencephalomalacia (PEM).
Nutritional PEM has traditionally been associated with thiamine (vitamin B1) deficiency in numerous animal species, particularly small carnivores and ruminants.Â While the pathogenesis and direct association with thiamine deficiency is well established in carnivores, the pathogenesis remains somewhat more obscure in ruminants who may be thiamine responsive early in disease, but often have striking PEM without a demonstrable deficiency in tissue thiamine, or blood transketolase levels.Â
In the early 1980s, nutritional PEM was first associated with elevated sulfur levels in a group of cattle in Missouri receiving sulfated feeds to limit feed consumption and has since been demonstrated in cattle, sheep, and goats receiving elevated sulfur from a variety of feed materials including sulfated feeds (calcium sulfate), high-protein forage (alfalfa), corn meal by-products, molasses based liquid feeds, sulfur containing plants, such as genus Brassica, and excessively sulfated water.(1)
The pathogenesis of sulfur-related PEM is related to ruminal microbes reducing ingested sulfur to highly toxic hydrogen sulfide, which then interferes with cellular energy metabolism.(2) Presumptively, the continuous energy requirement of cerebral neurons make them particularly susceptible.Â Additionally, sulfite, an intermediate in sulfate reduction, can cleave thiamine;(1) however, the contribution of this phenomenon to PEM in ruminants is not well established given the typically normal thiamine levels in these animals.Â
Clinical course in ruminants ranges from acute, characterized by acute cortical blindness, depression, dullness to recumbency, convulsions, opisthotonos, coma and death, to more subacute, characterized primarily by blindness and ataxia.Â Grossly cerebral edema, swelling, pallor and softening of the cerebrum with variable laminar paleness of the gray matter at the junction between gray and white is seen in acute deaths and tissues may autofluoresce under UV light.Â If survival is prolonged gross changes may progress to yellow-brown discoloration and cavitation of the gray matter and the tissue will fail to auto fluoresce.(2) Histologic lesions of PEM may be somewhat varied in their distribution, being more pronounced in the cerebral cortices of ruminants, and in periventricular nuclei of carnivores.Â Laminar cortical necrosis of neurons especially within the deeper laminae with malacia is classic.Â This change is also seen in cases of lead toxicity, hypoxia, and water deprivation-salt intoxication.(1)
Unlike in ruminants, the pathogenesis of nutritional PEM in carnivores (Chastek paralysis) is well established.Â Thiamine is an essential dietary vitamin in carnivores, and cases of PEM are associated with ingestion of high levels of thiaminase containing fish diets (cats) or consumption of excessively heated meats that destroy thiamine (dogs).Â Less commonly, consumption of the food preservative sulfur dioxide has been documented.Â The course of disease and clinical signs are similar to ruminants, with lesions more typically present bilaterally and symmetrically in the brain stem nuclei, most commonly the inferior colliculi.Â Less commonly the cerebral cortex and cerebellar vermis may be affected.Â Vascular dilation and hemorrhage may be a prominent feature.(3)
The clinical disease, histopathologic lesions and demonstration of elevated sulfur levels in the feed support a classic sulfur-related PEM in this bull.Â The source of sulfur is most likely the corn by-products (distillers grain) that can contain excessively high sulfur.Â The National Research Council states the daily requirement for adult beef cattle is 1500-2000 ppm sulfur within the ration with a daily maximum tolerated dietary dose of 0.4% (4000 ppm).(4)
Brain, cerebrum, cortex: Necrosis, laminar, multifocal, with diffuse spongiosis.
Conference participants discussed the causes of PEM in ruminants, as reviewed by the contributor in the above comments.Â Participants further discussed causes of polioencephalomalacia in other veterinary species, noting that the term polioencephalomalacia is generally used to describe softening in the cerebrocortical grey matter with a laminar distribution.Â There are several conditions associated with this pattern of necrosis, which is also referred to as laminar cortical necrosis or cerebrocortical necrosis.Â It is a characteristic lesion due to hypoxia/ischemia, such as that caused by feline ischemic encephalopathy due to aberrant migration of Cuterebra larva and neonatal maladjustment syndrome of foals, salt poisoning in swine, lead poisoning in cattle, and cyanide poisoning in a variety of species.(1)
1.Â Maxie MG, Youssef S.Â Nervous system.Â In: Maxie MG, ed.Â Pathology of Domestic Animals. 5th ed.Â Vol.Â 1.Â Philadelphia, PA: Elsevier Ltd, 2007;336-356.Â
2.Â Gould DH.Â Update on sulfur-related polioencephalomalacia.Â Vet Clin North Am Food Anim Pract. 2000;6:481-496, vi-vii.Â
3.Â Summers B, Cummings JF, Delahunta A.Â Degenerative diseases of the central nervous system.Â In: Veterinary Neuropathology. St.Â Louis, MO: Mosby; 1995:277-280.Â
4.Â Nutrient requirements of beef cattle/Subcommittee on Beef Cattle Nutrition, Committee on Animal Nutrition, Board on Agriculture, National Research Council.-ï¿½-ï¿½7th ed.Â Washington, DC., USA: National Academies Press, 2000;60-61.Â [http://www.ag.ndsu.edu/pubs/ansci/beef/eb74w.htm ]