7-month-old Aberdeen Angus bovine steer (Bos taurus)The animal presented for a short history of anorexia that progressed to ataxia, head pressing, and ultimately recumbency. Upon presentation, the calf was severely depressed, lethargic, unresponsive and severely ataxic in all four limbs. There was absence of menace reflex bilaterally, and the animal appeared to be blind. The owner stated that the calf was in a group of animals consuming a ration containing corn gluten.

Gross Description:  

Gross lesions were limited to the brain. There were multiple locally extensive areas within the cerebrum where the gray matter was markedly thinned. In these areas, remaining gray matter was characterized by fragmentation, softening and slight yellow to tan discoloration. Multifocally there was cleft formation at the gray matter-white matter junction where gray matter was separated from the underlying white matter (Figs. 1-1 and 1-2). When ultraviolet light was applied to the fresh brain, distinct autofluorescence of these areas was observed (Fig. 1-3). 

Histopathologic Description:

Multifocally the deep cortical gray matter adjacent to underlying white matter is disrupted, fragmented and rarefied in a laminar pattern. There is disruption, vacuolation and/or loss of the neuropil in these areas (malacia). There is loss of cortical neurons, and remaining neurons are often shrunken, angular, hypereosinophilic and contain pyknotic nuclei (neuronal necrosis) (Fig. 3-4). Multifocal remaining neurons are surrounded by glial cells (satellitosis and neuronophagia). Diffusely throughout the sections are increased numbers of glial cells (gliosis) including reactive astrocytes. In addition, there are multifocal random accumulations of erythrocytes (hemorrhage) and moderate numbers of gitter cells with fewer lymphocytes, neutrophils and in some sections karyorrhectic cellular debris. Axonal fibers are occasionally separated and surrounded by clear space (edema) and swollen axonal sheaths contain swollen hypereosinophilic bodies (spheroids) or gitter cells. Vessels are lined by plump endothelial cells (hypertrophy) and are frequently surrounded by clear space (edema) or moderate numbers of macrophages or lymphocytes. In some sections, the meninges are moderately expanded by clear space and low numbers of macrophages.

Morphologic Diagnosis:  

Brain (cerebrum): Necrosis and neuronal loss, cortical, laminar, multifocal, moderate to severe with moderate multifocal histiocytic and lymphocytic meningoencephalitis

Lab Results:  

Cerebral spinal fluid: Protein = 578.1 mg/dL; CK = 505 IU/L (normal range 0-5 IU/L); CSF cytology revealed mononuclear pleocytosis; blood lead was negative.



Contributor Comment:  

The gross and histologic lesions in the cerebrum of this calf are characteristic of nutritional polioencephalomalacia (PEM) that is commonly seen in growing ruminants. The pathogenesis of nutritional PEM associated with thiamine deficiency is well established in carnivores (progressive encephalopathy); a thiamine-PEM association in ruminants is less clear. PEM in ruminants was thought at one time to be exclusively caused by thiamine deficiency, but it is now known that the laminar cortical necrosis can be caused by sulfur toxicity, lead toxicity, and hypoxia in addition to thiamine deficiency.(2) Confusion regarding the cause of PEM in cattle is partly due to the lack of a method to accurately evaluate thiamine status in animals as well as thiamine-responsiveness that is frequently noted clinically. 

The basis of sulfur-associated PEM in ruminants appears to be the excessive production of ruminal sulfide caused by the ruminal microbial reduction of ingested sulfur. Soluble hydrosulfide anion is in the rumen fluid phase, and hydrogen sulfide gas accumulates in the rumen gas cap. Non-reduced forms of sulfur (sulfate and elemental sulfur) are relatively nontoxic, while hydrogen sulfide and its ionic forms are highly toxic substances that interfere with cellular energy metabolism.(1) Sulfide inhibits cellular respiration by blocking cytochrome C oxidase in the electron transport chain. It is likely that sulfide produced in the rumen is absorbed into the blood and is capable of inhibiting energy metabolism of neurons and that this either directly causes neuronal necrosis or leads to necrosis by interfering with local cerebral blood flow and creating regional ischemia.(3) The most important route of sulfide absorption is unknown, but potentially occurs via the gastrointestinal mucosa or pulmonary mucosa after inhalation of eructated ruminal gas. The role of thiamine in these cases is not completely clear; however most current evidence indicates that sulfur-associated PEM does not involve reduced concentrations of thiamine in blood/tissues or reduced activity of transketolase, a thiamine-dependent enzyme.(3) A significant portion of PEM cases in ruminants may in fact be sulfur-associated rather than thiamine-associated, as was once thought.

Exposure to large amounts of sulfur can occur from a variety of sources including both feed and water. The occurrence of PEM in ruminants associated with high dietary sulfur intake has been recognized with increasing frequency, particularly in Midwestern United States. This appears to be associated with the recent expansion of the fuel ethanol industry, as byproducts of corn (maize)-to-fuel ethanol production are being used with increasing frequency in ruminant diets. Ethanol byproducts are attractive feed ingredients due to their nutritional (especially protein) value and they are readily available at reduced cost (compared to corn) in Midwestern states. Sulfuric acid is utilized in ethanol byproduct production, and byproducts thus often contain significantly elevated levels of sulfur which represent a major source of dietary sulfur for these animals. In addition, there is much variation in the sulfur content of ethanol byproducts both within and between plants, and for this reason periodic monitoring is recommended for producers utilizing these products in rations.(2) In this case, the history of corn gluten meal feeding (a commonly fed ethanol byproduct) is considered to be the likely source of elevated sulfur, though feed samples were not evaluated for confirmation. This case represents a classic case of ruminant PEM both clinically and pathologically. Sulfur-related PEM manifests clinically as acute blindness, recumbency, seizures and death or a more subacute form characterized by visual impairment and ataxia. Lesions are classic and are characterized by extensive necrosis of cerebrocortical neurons. Grossly, there is fragmentation, malacia and loss of cortical gray matter that in some cases autofluoresces brightly when exposed to 366-nm UV light. At later stages, affected tissue becomes cavitated as macrophages infiltrate and necrotic tissue is removed.(1)

JPC Diagnosis:  

Brain, cerebrum: Necrosis and neuronal loss, cortical, laminar, multifocal, moderate to severe, with edema and moderate multifocal histiocytic and lymphocytic meningoencephalitis

Conference Comment:  

The contributor does a magnificent job describing PEM in ruminants. Thiamine deficiency in carnivores (Chastek paralysis) is also mentioned and a brief review follows.

Thiamine, or vitamin B1, is an essential dietary need in carnivores. Ruminants are able to produce their own thiamine from the diet via microbial production in the rumen.(3) Thiamine deficiency in carnivores often results from eating a diet high in fish containing thiamine-splitting enzymes (thiaminases). Sulfur dioxide, often used to preserve that fresh fish appearance, can destroy thiamine after it is metabolized into sulfates.(3)

If the disease is recognized early in its progression, thiamine supplementation can reverse the course of the disease. If clinical signs are present for several days, and a point of no return is passed, death is the result. Microscopic lesions include vacuolation of the neuropil, vascular dilation, hemorrhage, and necrosis. The periventricular gray matter is highly susceptible and the lesion is almost always bilateral and symmetrical most often involving the inferior colliculi.(3)


1. Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, IA website. Polio in cattle can be caused by sulfur toxicity. Accessed July 05, 2008
2. Gould, D: Update on sulfur-related polioencephalomalacia. In: The Veterinary Clinics of North America: Food Animal Practice: Toxicology, eds. Osweiler GD and Galey FD. pp 481-496. 16(3): November 2000
3. Maxie MG, Youssef S: Nervous system. In: Jubb, Kennedy and Palmers Pathology of Domestic Animals, ed. Maxie MG, 5th ed., vol 1, pp.351-356. Elsevier Limited, Philadelphia, PA, 2007
4. McAllister, MM: Feed-Associated toxicants: sulfur. In: Clinical Veterinary Toxicology, ed. Plumlee K, pp 133-134. Mosby, St Louis, MO, USA, 2004

Click the slide to view.

3-1. Cerebrum, ox

3-2. Cerebrum, ox.

3-3. Cerebrum, ox

3-4. Cerebrum, ox

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