Also known as
Cerebrocortical necrosis (CCN)
Polioencephalomalacia (PEM) literally means softened grey matter of the brain. Often the term Cerebrocortical necrosis (CCN) is used interchangeably with PEM.
Polioencephalomalacia is a common neurologic disease of ruminants and can be caused by thiamine deficiency which affects the brain.
The main clinical signs result from dysfunction of the cerebrum and include wandering, circling, blindness (total or partial loss of vision in a normal-appearing eye caused by damage to the brain), incoordination, head pressing, recumbency, rapid involuntary eye movements, backward arching of head and neck, seizures, disoriented movement, and eventual death, if left untreated.
Onset of PEM can occur at any age.
Clinical signs of PEM are variable depending on the area of the brain affected. Some animals are simply found dead before disease signs are noticed.
Polioencephalomalacia may be acute or subacute. Animals with the acute form often show blindness followed by recumbency, seizures, and coma. If found soon enough, they can often be treated and recover.
Those with a longer duration of acute signs have poorer responses to therapy and higher mortality. Animals with the subacute form usually leave the herd, stop eating, and display twitches of the ears and face. The head is held in an elevated position. The animal seems blind but the pupils of the eyes have normal light reflex.
The animal is uncoordinated and sometimes moves with exaggerated gait. Head pressing and grinding of the teeth may also be seen.
The subacute form 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 have significant neurologic impairment that necessitates culling.
Diagnosis is often difficult, but often suspected, based on combination of neurologic signs, elimination of other diagnoses, and response to thiamine administration—but this response is inadequate for a definitive diagnosis.
Thiamine is a key chemical in glucose metabolism. If an animal is deficient, neurological activity is impaired. Diagnostic tests include blood thiamine levels, and in cases of suspected sulfur-induced polioencephalomalacia, by checking the sulfur content in feed and water.
Diseases and conditions with similar signs include acute lead poisoning, water deprivation and sodium toxicosis, Histophilus meningoencephalitis, rabies,
coccidiosis with nervous involvement, and vitamin A deficiency. These must be ruled out when making a diagnosis.
Polioencephalomalacia is seen sporadically in individual animals or as a herd outbreak. Younger animals are more frequently affected than adults.
Pastured animals can develop PEM, but animals on high-concentrate diets are at higher risk, as are cattle exposed to high levels of sulfur in water, feed (rations with byproducts of corn or beets processing), or a combination of sources. The patterns of PEM occurrence depend on the various factors involved.
A beneficial response to thiamine therapy by PEM-affected animals is sometimes considered evidence of thiamine deficiency. This thiamine-responsiveness is often seen if treatment is begun early in the course of the disease, but PEM is also associated with high sulfur intake.
Diagnosis can be confirmed by necropsy. The pattern of clinical signs should arouse suspicion of polioencephalomalacia, but at necropsy the characteristic lesions are evident.
- Head pressing,
- Rapid involuntary eye movements,
- Backward arching of the head and neck,
- Disoriented movement,
- Lack of appetite
- Muscle tremors
- Teeth grinding
Young animals that do not yet have a functioning rumen depend on dietary thiamine. If it is lacking in their diet they may develop PEM. In adult ruminants, thiamine is produced by rumen microbes. Under normal conditions, ruminants don’t need to eat thiamine-rich foods.
Thiamine inadequacy in adults can be caused, however, by decreased or altered production by rumen microbes (which can happen when high-concentrate feeds are fed) or factors that interfere with the action of thiamine, such as plant thiaminases (enzymes that break down or make thiamine inactive).
Thiaminases enzymes can also be produced by gut bacteria or ingested as preformed plant products. They can either destroy thiamine or form antimetabolites that interfere with thiamine function. High grain intake enables one such harmful microorganism to proliferate.
A neurologic disorder diagnosed in Australia has been associated with the Nardoo fern, which may contain high levels of a thiaminase I enzyme. Other ferns, such as bracken and rock fern, contain a similar thiaminase I. PEM has been produced experimentally by feeding high doses of extracts of these plants, but actual cases are uncommon, because these plants are unpalatable to cattle and they rarely eat them unless they are baled up in hay.
Thiamine (vitamin B1) is essential for glucose metabolism. Glucose is the most important form of energy for the brain. Ruminants do not depend on dietary sources for vitamin B1, as these vitamins are readily synthesized by the rumen microbes.
However, in PEM cases, increased thiaminase type 1 levels are found in rumen fluid and this enzyme not only rapidly destroys thiamine, but also leads to production of active antagonists (molecules that get in the way of chemical processes), which further deplete thiamine in the blood and body tissues.
This destructive enzyme (thiaminase type 1) is produced in the rumen by certain bacteria, such as Clostridium sporogenes and Bacillus thiaminolyticus. These organisms multiply under conditions in which production of volatile fatty acids is reduced, such as when cattle consume lush, low-fiber forages and high concentrate diets.
The presence of thiaminases counter the production of thiamine by breaking them down. Eventually, when the rate of synthesis production cannot exceed thiaminase production or intake, a state of thiamine deficiency is reached.
Some forages, such as bracken rhizomes, horsetail, and Mexican fireweed (Kochia) contain thiaminase type 1 and might occasionally be consumed by cattle under certain situations, as when baled in hay. There is also evidence that treatment with certain deworming drugs (levamisole and thiabendazole) may predispose cattle to PEM.
Since glucose metabolism is regulated by thiamine, overconsumption of glucose can also result in thiamine inadequacy. With a sudden increase of glucose in the body, thiamine is depleted and not available when the next round of glucose needs to be metabolized.
Excess dietary sulfur, particularly in the form of malted barley, and excess copper have also been associated with this disease. Sulfur is needed for synthesis of important sulfur-containing amino acids and their contribution to synthesis of various hormones, enzymes, and structural proteins, but too much sulfur is harmful.
In ruminants, the same rumen microbes that generate thiamine molecules reduce sulfur into toxic sulfides. Among the sulfide toxins is hydrogen sulfide, a gas compound that competes with oxygen to bind with red blood cells and eventually enters the brain to disrupt neural activity.
The basis of sulfur-related PEM appears to be production of excessive ruminal sulfide due to the ruminal microbial effects on ingested sulfur. Hydrogen sulfide gas (H2S), which has the odor of rotten eggs, accumulates in the rumen gas.
Although sulfate and elemental sulfur are relatively nontoxic, H2S and its various ionic forms are highly toxic and interfere with cellular energy metabolism. The central nervous system (which depends on a high and uninterrupted level of energy production), can be significantly affected by energy deprivation.
When cattle start consuming feed or water with high sulfur content, ruminal sulfide concentrations peak 1 to 4 weeks after the change. This pattern is probably due to alterations in rumen microflora. The occurrence of PEM peaks during the time period when ruminal sulfide concentrations are highest. Animals with sulfur-associated PEM do not have altered thiamine status.
A variety of sulfur sources can result in excessive sulfur intake, including water, feed ingredients, and forage. The water in many geographic areas contains sulfate. When evaporation occurs, water sulfate concentrations increase.
Water consumption by cattle increases in hot weather, leading to increased sulfur intake due to concurrent increases in water consumption and increased sulfate concentrations in the water.
Alfalfa, with its high protein and sulfur-containing amino acid content, can also be a significant source of sulfur. Grasses tend to be low in sulfur, but some circumstances can result in high sulfate concentrations. Certain weeds, including Canada thistle, kochia, and lambsquarter, can accumulate sulfate.
Cruciferous plants (which include turnips, rape, mustard, and oil seed meals) normally synthesize sulfur-rich products and can be sources of excess sulfur. Byproducts of corn, sugar cane, and sugar beet processing commonly have high sulfur content.
PEM has been associated with use of these types of byproducts as feed ingredients. Corn-based ethanol production has resulted in increased availability of corn byproducts that may vary widely in sulfur content.
Wet distillers grains plus solubles may have sulfur content ranging from 0.44%–1.74% sulfur as dry matter. A high molasses-urea diet has been associated with a form of PEM without altered thiamine status.
PEM signs are sudden and acute if ingested toxic plants, toxic levels of sulfur or sudden ruminal acidosis occurs. Signs may not appear until 2 or 3 weeks after the change of diet causes development of subclinical ruminal acidosis, and may appear within 15 to 30 days if cattle are exposed to high dietary sulfur. In calves with low intake, there may be longer term chronic onset, and you may see other signs of ill thrift first.
Animals most commonly affected are calves 6-18 months of age, though calves 2 to 12 month of age are considered at greatest risk, depending on feed practices—such as low amount of dietary roughage, high-sulfate ration, molasses-urea diet, and cobalt-deficient diet. Feeding cattle high levels of amprolium (as treatment or prevention for coccidiosis) may cause similar problems, as can acepromazine sedation.
PEM is sometimes seen in well-nourished calves that have been deprived of feed for a period due to poor pasture conditions, and in animals on diets with high sulfur content, and animals on high concentrate rations. While only a small proportion of the herd or group might be affected, those affected animals are likely to die, unless treated early.
Dietary ingredients or water with high sulfur concentration should be avoided or very gradually introduced to improve the chances of successful adaptation. Cattle should be fed a diet with at least 60% of the dry matter being fresh or conserved green forage to reduce risks for thiamine problems.
Be aware of risks associated with grazing bracken or having it end up in hay, and the risks associated with animals that start grazing after a long period without grass or on a reduced diet (particularly following long and severe periods of rainfall).
Do not use ammonium sulfate as an acidity regulator in vitamin/mineral premixes, if these are used on the farm.
During an outbreak, sufficient roughage should be provided. If the problem is 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 supplementation of thiamine at 3-10 mg per kg of feed has been recommended for prevention when animals are on high-concentrate diets, or allowing access to pasture or good-quality green hay.
Early administration of thiamine may provide dramatic response, but if the condition is advanced, the surviving animals may remain partially blind and mentally impaired.
If cases do occur, other animals in the group should be supplemented with thiamine until normal rumen fermentation is re-established. Oral treatment with the less water soluble thiamine derivatives, such as thiamine propyl disulfide or thiamine tetrafurfuryldisulfide, is the best option, as these do not get destroyed by thiaminase and are readily absorbed from the gut.
Affected individuals should be treated with high levels of thiamine HCl (10-15 mg per kg of body weight, administered intravenously every 6 hours) or multi-B vitamin preparations given by IV every three to four hours until the animal has recovered. This usually results in significant improvement in 24 hours (often within 6 to 8 hours). Therapy should continue every 6 to 12 hours for 2 more days, and recovery may take as long as a week.
The first dose is administered very slowly by IV; otherwise, the animal may collapse. Subsequent doses can be administered intramuscularly for 3–5 days. Therapy must be started early in the disease course; if brain lesions are severe or treatment is delayed, full recovery may not be possible.
Beneficial effects are usually seen within 24 hours and sometimes sooner. If there is no initial improvement, treatment should be continued for up to 3 days. Reduction of cerebral edema can be attempted with administration of dexamethasone intramuscularly or subcutaneously. Therapy for convulsions may be necessary.
Seizures can usually be controlled with a barbiturate or diazepam. Mannitol (20% solution) can be given IV. DMSO (40% solution given IV), or dexamethasone (1-2 mg per kg of body weight, given IV) may also be useful in reducing cerebral edema.
The affected animal should be isolated in a quiet, well bedded pen, with feed and water readily available. Make sure the animal takes in fluid and does not dehydrate; provide fluid via stomach tube if necessary. Good nursing can aid recovery. If there is no improvement, euthanasia should be considered in patients not responding to treatment within 3 days.
PEM resulting from eating high-sulfur diets such as barley malt sprouts, corn byproducts, molasses-based supplements, or Brassica oleracea (cabbage family of plants) may not respond to thiamine supplementation, and patients with cortical necrosis may not regain vision.