Sulfur-related polioencephalomalacia (PEM) is a common neurologic disease of ruminants that is frequently associated with a high total sulfur intake. Although initial studies indicated that PEM is caused by thiamine deficiency, our studies show that PEM, in many instances, is a form of sulfide neurotoxicity. PEM is characterized by necrosis and subsequently malacia, of cerebrocortical tissue. During the stage of necrosis grossly evident autofluorescence occurs with 366 nm ultraviolet illumination. At later stages the affected cortical tissue undergoes cavitation as macrophages infiltrate and necrotic tissue is removed. This cavitation is often grossly observable. The signs occur in 2 clinical forms. One is acute and characterized by visual impairment, recumbency, seizures, and often death. The other form is more subacute and characterized by visual impairment and ataxia. This form is often called blind staggers in range cattle.

The onset of the clinical signs of PEM coincides with an episode of excessive ruminal sulfide production. It is possible to measure of ruminal gas cap H₂S concentration, and this makes it possible to identify cattle with potentially hazardous total sulfur intake. It appears that the basis of sulfur-related PEM is the production of excessive ruminal sulfide due to the ruminal microbial reduction of ingested sulfur. Soluble hydrosulfide anion is in the rumen fluid phase and hydrogen sulfide (H₂S) gas accumulates in the rumen gas cap. H₂S has the odor of rotten eggs. Non-reduced forms of sulfur such as sulfate and elemental sulfur are relatively non-toxic, whereas H₂S and its various ionic forms are highly toxic substances that interfere with cellular energy metabolism.

Evaluation of all potential sulfur sources is necessary to estimate total dietary sulfur concentration and detect excessive sulfur intake. This information can lead to prevention strategies. Potential sources of sulfur include naturally occurring sulfate in water, a situation common in many livestock-raising areas of the world. Grasses tend to be low in sulfur; although, under some circumstances, grasses can be high in sulfate. Certain weeds seem to be able to accumulate large amounts of sulfate. Cruciferous plants (turnips, kale, rape, canola) constitutively produce glucosinolates, which have 2 sulfur atoms per molecule. Co-products of corn, sugar cane, and sugar beet processing commonly have a high sulfur content. Assessing potential excesses in sulfur intake requires estimation of total sulfur concentration of dry matter consumed from all sources, including water. By comparing this estimate to the maximum tolerable sulfur concentration for beef cattle (0.4% sulfur as dry matter), it is possible to evaluate potential hazards. Even though thiamine status alterations have not been observed with sulfur-associated PEM, thiamine treatment can have non-specific beneficial effects.