Polioencephalomalacia: Introduction
(Cerebrocortical necrosis) |  |
| Polioencephalomalacia (PEM) is an important neurologic disease of ruminants that is seen worldwide. Cattle, sheep, goats, deer, and camelids are affected. The term PEM denotes a lesion with certain gross and microscopic features that are not specific for a particular etiology or pathogenesis. Historically, PEM has been associated with altered thiamine status, but more recently an association with high sulfur intake has been observed. Other toxic or metabolic diseases (eg, acute
lead poisoning, sodium toxicosis/water deprivation) can result in PEM as well. |
| Etiology, Pathogenesis, and Epidemiology: |
| The disease is seen sporadically or as a herd outbreak. In general, younger animals are more frequently affected than adults. Animals on high concentrate diets are at higher risk, but pastured animals also develop PEM. Cattle fed rations with added sulfate to limit intake or with byproducts of corn or sugar cane processing are at higher risk. The patterns of PEM occurrence depend on the etiologic factors involved. |
| PEM has been associated with 2 types of dietary risks: altered thiamine status and high sulfur intake.
Thiamine inadequacy in animals with PEM has been suggested by several types of observations, including decreased concentrations of thiamine in tissues or blood and deficiency-induced alterations of thiamine-dependent biochemical processes (decreased blood transketolase activity, increased thiamine pyrophosphate effect on transketolase, and increased serum lactate). Unfortunately, many of these biochemical features of
altered thiamine status are inconsistently observed in cases of PEM. |
| Thiamine inadequacy can be caused by such factors as acute dietary deficiency of thiamine or ingestion of plant thiaminases or thiamine analogs. A potential mechanism of thiamine inadequacy is the action of thiaminases on thiamine in the GI tract. Thiaminases can be produced by gut bacteria or ingested as preformed plant products. They can either destroy thiamine or form antimetabolites that interfere with thiamine function. Thiaminase I, produced by
Bacillus
thiaminolyticus
and
Clostridium
sporogenes
, and thiaminase II, produced by
B
aneurinolyticus
, catalyze the cleavage of thiamine. The latter microorganism proliferates under conditions of high grain intake. |
| A neurologic disorder in Australia has been associated with the Nardoo fern (
Marsilea
drummondii
), which may contain high levels of a thiaminase I enzyme. Other ferns such as bracken (
Pteridium
aquilinum
) and rock fern (
Cheilanthes
sieberi
) contain a similar thiaminase I. Although PEM has been produced experimentally by feeding high doses of extracts of such plants, field cases are uncommon because these plants are unpalatable (see also
Bracken Fern Poisoning : Introduction). |
| Overall, there is not a linear relationship among the presence of ruminal and fecal thiaminase, decreased concentrations of tissue and blood thiamine, and development of disease. |
| A beneficial response to thiamine therapy by PEM-affected animals is sometimes considered evidence of thiamine inadequacy. This thiamine-responsiveness is often seen if treatment is initiated early in the course of the disease. The assumption that this response indicates that deficiency of thiamine is the true etiology should be viewed with caution, however. Large doses of thiamine, beyond maintenance needs, may have nonspecific, beneficial effects in the energy-impaired brain. |
| PEM associated with
high sulfur intake is recognized with increasing frequency. The basis of sulfur-related PEM appears to be the production of excessive ruminal sulfide due to the ruminal microbial reduction of ingested sulfur. Hydrogen sulfide (H2S) gas, which has the odor of rotten eggs, accumulates in the rumen gas cap. Concentrations can be demonstrated with commercially available H2S detection
tubes via percutaneous gas sampling. While nonreduced forms of sulfur, such as sulfate and elemental sulfur, are relatively nontoxic, H2S and its various ionic forms are highly toxic substances that interfere with cellular energy metabolism. The CNS, by virtue of its dependence on a high and uninterrupted level of energy production, is likely to be significantly affected by energy deprivation. When cattle undergo a transition to high sulfur intake, ruminal
sulfide concentrations peak 1-4 wk after the change. This pattern is probably due to alterations in ruminal microflora. PEM peaks during the time period when ruminal sulfide concentrations are the highest. |
| A variety of sulfur sources can result in excessive sulfur intake, including water, feed ingredients, and forage. Many geographic areas have surface and deep waters high in sulfate. When evaporation occurs, water sulfate concentrations increase. Water consumption by cattle is temperature dependent and increases greatly at high temperatures, leading to increased sulfur intake due to concurrent increases in water consumption and sulfate concentrations in water. Alfalfa, by virtue
of its high protein and sulfur-containing amino acid content, can serve as a significant source of sulfur. Although grasses tend to be low in sulfur, some circumstances can result in high sulfate concentrations. Certain weeds, including Canada thistle (
Cirsium
arvense
), kochia (
Kochia
scoparia
), and lambsquarter (
Chenopodium
spp) can accumulate sulfate in high concentration. Cruciferious plants normally synthesize sulfur-rich products and serve as important sources of excess sulfur. These include turnips, rape, mustard, and oil seed meals. Byproducts of corn, sugar cane, and sugar beet processing commonly have a high sulfur content, apparently due to the addition of sulfur-containing acidifying agents. PEM has been associated with the use of these types of byproducts as feed ingredients.
A high molasses-urea diet has been associated with a form of PEM that lacks altered thiamine status. |
|  |
| Clinical Findings: |
| PEM may be acute or subacute. Animals with the acute form manifest blindness, recumbency, tonic-clonic seizures, and coma. Those with a longer duration of acute signs have poorer responses to therapy and higher mortality. Animals with the subacute form initially separate from the group, stop eating, and display twitches of the ears and face. The head is held in an elevated position and there is a staggering, sometimes hypermetric gait. As the disease progresses, there is
cortical blindness with a diminished menace response and unaltered palpebral and pupillary responses. Dorsomedial strabismus may develop. Head pressing, opisthotonos, and grinding of the teeth may be observed. The subacute form of PEM is frequently followed by recovery with only minor neurologic impairment. However, in a few cases, the subacute form may progress to a more severe form with recumbency and seizures. Animals that survive the acute form or advanced subacute form often
manifest significant neurologic impairment that necessitates culling. |
Lesions:
| Gross lesions are inconsistent and frequently subtle, especially early in the disease. Acutely affected animals may have brain swelling with gyral flattening and coning of the cerebellum due to herniation into the foramen magnum. Slight yellowish discoloration of the affected cortical tissue may be present. The brains of acutely affected animals may also have autofluorescent bands of necrotic cerebral cortex evident on meningeal and cut surfaces of the brain when viewed
with ultraviolet illumination. As the pathologic process progresses, the affected cerebrocortical tissue has macroscopically evident cavitation, sometimes sufficient to result in apposition of the pia meninges to the white matter. |
|
The initial histologic lesions are necrosis of cerebrocortical neurons. The neurons are shrunken and have homogeneous, eosinophilic cytoplasm. Nuclei are pyknotic, faded, or absent. Cortical spongiosis is sometimes present in the early phases of the acute form. Vessel cells undergo hypertrophy and hyperplasia. At later stages, the affected cortical tissue undergoes cavitation as macrophages infiltrate and necrotic tissue is removed. A
pattern observed in brains of cattle with early, severe, acute sulfur-related PEM features multifocal vascular necrosis, hemorrhage, and parenchymal necrosis in deep gray matter including the striatum, thalamus, and midbrain. |
| |
| Diagnosis: |
| The pattern of clinical signs should arouse suspicion of PEM. At necropsy, macroscopically evident cerebrocortical autofluorescent areas under ultraviolet illumination provide a presumptive diagnosis of PEM. Characteristic histologic lesions are confirmatory. |
| Differential diagnoses for cattle include acute lead poisoning, water deprivation/sodium toxicosis,
Histophilus
meningoencephalitis, rabies, coccidiosis with nervous involvement, and vitamin A deficiency. Differential diagnoses for sheep include pregnancy toxemia, type D clostridial enterotoxemia (focal symmetric encephalomalacia), and listeriosis. |
| Confirmation of etiology or pathogenesis requires laboratory testing of samples from affected animals or their environment. Assessment of thiamine status is difficult and results should be interpreted with caution. Few laboratories are capable of measuring thiamine content of blood and tissues, transketolase activity, or the thiamine pyrophosphate effect on transketolase. Demonstration of clinical improvement after thiamine therapy is not adequate evidence for a specific
diagnosis. The possibility of sulfur-associated PEM can be assessed by measuring the sulfur content of the water and dietary ingredients and then estimating the total sulfur intake on a dry-matter basis. The maximal tolerated concentration of sulfur is considered to be 0.4% dry matter. Because multiple factors are involved in determining the actual risk of developing PEM, this concentration should not be considered an absolute maximum. Many cattle adapt adequately to sulfur
intake levels > 0.4%, although negative effects, possibly subclinical, on performance may occur. |
| |
| Treatment and Prevention: |
| The treatment of choice regardless of cause is thiamine. Therapy must be started early in the disease course for benefits to be achieved. If brain lesions are particularly severe or treatment is delayed, full clinical recovery may not be possible. The dosage of thiamine is 10-20, mg/kg, IM or SC, tid. Initial treatment may be administered IV. Beneficial effects are usually observed within 24 hr and sometimes sooner; however, if there is no initial improvement,
treatment should be continued for 3 days. Reduction of cerebral edema can be attempted with administration of dexamethasone at a dosage of 1-2 mg/kg, IM or SC. Symptomatic therapy for convulsions may be necessary. |
| Dietary supplementation of thiamine at 3-10 mg/kg feed has been recommended for prevention, but the efficacy of this approach has not been carefully evaluated. During a PEM outbreak, sufficient roughage should be provided. When the problem could be associated with high sulfur intake, all possible sources of sulfur, including water, should be analyzed and the total sulfur concentration of the consumed dry matter estimated. Dietary ingredients or water with high sulfur
concentration should be avoided; if this is not possible, then more gradual introduction to the new conditions can improve the chances of successful adaptation. |
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