Polioencephalomalacia in Cattle
Polioencephalomalacia (PEM) of ruminants is a neurological disorder, characterized by cerebrocortical necrosis. PEM has been involved with thiamine deficiency, sulfur intoxication and other less common factors include lead poisoning and water-deprivation-sodium ion toxicosis. In this study, the clinical signs, pathological findings and etiopathogenesis of PEM in ruminants are reviewed.
February 20, 2010; Accepted: March 29, 2010;
Published: July 10, 2010
Polioencephalomalacia (PEM) or cerebrocortical necrosis is a neurologic disease
of ruminants characterized by necrosis of cerebral cortex (Loew
et al., 1969; Summers et al., 1995).
PEM affects young ruminants, usually 2 to 7 months/sheep and from weaning at
6 to 18 months/cattle. Adults animals can also develop it although more sporadically.
Several causes have been associated with this disease, including thiamine deficiency,
sulfur intoxication, acute lead poisoning and water deprivation-sodium ion toxicosis
(Pandher, 2000). Sudden changes in diet (from poor to
good pasture, or supplementation, or sudden increase in carbohydrates), administration
of oral antibiotics and/or coccidiostats (Amprol plus), water deprivation and
even eating carcasses has also been incriminated as triggering factors (Radostits
et al., 2007). The diagnosis of PEM usually is based on clinical
signs, history of the herd management and laboratory analysis (levels of blood
lactate, pyruvate and thiamine, glycemia, transketolase activity in red blood
cells) (Edwin et al., 1979; Horino
et al., 1994). Differential diagnosis includes rabies, Aujesky disease
(Callan and van Metre, 2004), BHV-5 (Aquino
Neto et al., 2009), cerebral babesiosis (Everitt
et al., 1986), enterotoxemia (Filho et al.,
2009), hepatic encephalopathy (West, 1997), plant
poisoning and tetanus (Summers et al., 1995).
CLINICAL SIGNS AND PATHOGENESIS
PEM is characterized by progressive neurological signs including blindness, ataxia, listlessness, proprioceptive deficits, circling, recumbency, muscular incoordination, t nystagmus, head pressing against solid objects, convulsions, coma and death. Symptoms seem to be associated with increased intracranial pressure that accompanies brain edema and necrosis of neurons. Death usually occurs 2-3 (sometimes up to 12) days after the onset of signs. Treatment with thiamine may have an effect if started early. The mainly causes and mechanisms involved in the developing of PEM are described below.
Thiamine deficiency: Thiamine (vitamin B1) is an important coenzyme
in several pathways of intermediate metabolism of carbohydrates and energy in
organisms. This vitamin is essential for brain function and its deficiency causes
decreased levels of thiamine diphosphate (ThDP), an indispensable cofactor for
several key enzymes in cell energy metabolism, especially pyruvate and oxoglutarate
dehydrogenases and transketolase. In ruminants, thiamine is produced by ruminal
bacteria and protozoa under normal environmental conditions. Disruptions in
the normal rumen microbial population can promote a thiamine-deficient state.
Thiamine deficiency is related to overeating, acute impaction, grain engorgement,
founder and grain overload (Harmeyer and Kollenkirchen,
1989). Acidosis can promote proliferation of thiaminase II producing bacteria
(C. sporogenes and Bacillus sp.) (Brent, 1976).
This enzyme destroys thiamine, producing a thiamine analog that inhibits thiamine-dependent
reactions of glycolysis and decarboxylations (Brent and
Bartley, 1984). It has been known that thiamin analogs in the presence of
a cosubstrate are responsible for PEM development. PEM can also be caused by
thiaminase I (Edwin and Jackman, 1970). Several drugs
including promazines, levamisole, benzimidazoles act as a cofactor to thiaminase
I. This enzyme is also present in different plants such as horsetail (Equisetum
arvense), bracken fern (Pteridium aquilinum) (Vetter,
2009), prostrate pigweed (Amaranthus blitoides)(Ramos
et al., 2005), small flowered mallow (Malva parviflora) (Main
and Butler, 2006), kikuyu grass (Pennisetum clandestinum) (Bourke,
2007), Medicago sativa (Meyer, 1989) and Nardoo
fern (Marsilea drummondii) (Pritchard et al.,
1978). Amprolium, an anticoccidial drug can promote PEM in cattle, acting
as a thiamine antagonist. This drug inhibits thiamine metabolism and ThDP biosynthesis
leading to neuronal cell loss (Rindi et al., 2003;
Chornyy et al., 2007). Experimental studies in calves showed that
oral administration of amprolium (600 mg/kg/day) promotes neurological signs
and pathological findings of cerebrocortical necrosis. Blood and tissue thiamine
levels decreased, especially in cerebrum and cerebellum (Kasahara
et al., 1989; Horino et al., 1994).
Sulfur-associated polioencephalomalacia: This disorder has been more
recently and frequently described in the literature. The excess of sulfur in
diet is one of the related causes of sulfur-associated PEM. The major dietary
sulfur sources are alfafa hay, molasses, beet pulp, barley malt sprouts, calcium
sulphate, ammonium sulphate, sodium sulphate and grain-processing products (corn
gluten meal, brewers grain) (NRC, 2001). The recommended
maximum rate of sulfur on diet is 0.5% for cattle eating more than 40% forage
(Klasing et al., 2005). On the other hand, when
dietary sulfur is as low as 0.35% cattle on diets containing less than 15% forage,
cattle can develop PEM. Younger beef cattle and lactating cows seem to be more
susceptible to excess sulfur intake (Sager et al.,
1990; Kung et al., 1998; Loneragan
et al., 1998). Experimentally, diets with high concentrations of
sulfate has been reproduced PEM. It was demonstrated that the onset of clinical
signs presents in animals with sulfur-related PEM coincided with excessive ruminal
sulfide production (Gould, 1998). The sulfite produced
during the reduction of sulfate to sulfide cleaves thiamine at the methylene
bridge; thus, high sulfide levels could cause the brain lesions associated with
Acute lead poisoning (plumbism): Lead (Pb) is a highly toxic heavy metal
found in all parts of the environment. There are different forms of lead: metallic
lead, inorganic lead and lead compounds (or lead salts) and organic lead (containing
carbon). The main sources of lead include batteries, discarded crankcase oil,
asphalt, paint and solder. These products can contaminate pastures or feeds
during storage and processing (Van Beek et al., 1992;
Lemos et al., 2004). The lead is rapidly absorbed
in the gut and distributed to blood and tissues (Humphreys,
1991). The nervous tissue is especially sensitive to the effects of lead.
Several experiments with rodents exhibited the direct neurotoxic actions of
lead by apoptosis (programmed cell death), excitotoxicity affecting neurotransmitter
storage and release and altering neurotransmitter receptors, mitochondria, second
messengers, cerebrovascular endothelial cells and both astroglia and oligodendroglia
(Liu et al., 2010). The duration to exposure
depends of the chemical form of the lead. Lead sulphate and particulate lead
promotes temporary, but very high exposure and poisoning after the ingestion
of battery fragments. On the other hand, exposure to metallic lead is extended
because it is retained in the rumen (Sharpe and Livesey,
2004). One studied demonstrated that tissue Pb was significantly higher
in calves on a milk diet compared to tissue from calves on a grain and hay diet
(Zmudzki et al., 1984). Neurological signs typically
occur after a single ingestion of a material containing a large quantity of
lead (Oskarsson et al., 1992). The affected animals
can present blindness, facial tremors, progressive recumbency and chewing gum
seizures (Osweiler et al., 1985).
Water deprivation-sodium ion toxicosis: PEM can occur sporadically in
cattle subjected to water restriction. This disorder can be due to blood sodium
imbalance in cases of water deprivation followed by unrestricted imbibition
(Carmalt et al., 2000). The water restriction
can be caused by broken pumps, overturned water tubs, frozen water and moldy
bottles, for example. Access to salt or salt-containing water exacerbates the
effects of water restriction (Sandals, 1978). The increase
in serum concentration of sodium leads to water movement from the brain intracellular
space to the extracellular compartment. Large shifts in brain water content
can decrease brain volume and predispose to vascular damage and irreversible
neurologic injury. High concentrations of sodium in the central nervous system
can also impede anaerobic glycolysis with consequent inhibition of sodium export.
The affected animals reveal right lateral recumbency, rumen tympany, convulsions,
opisthotonus, horizontal nystagmus, champing of the jaws, generalized tremors,
abdominal pain and polydipsia. Some animals can also present diarrhea and blindness
(Senturk and Huseyin, 2004). The recommend limit of
salt is 4% in feed and 0.3% in water (Pearson and Kallfelz,
Lesions vary accordingly to the intensity and duration of disease. In the early
phase of the disease, the damaged tissue autofluoresces under ultraviolet (360
nm) illumination. Progressively, the affected tissue becomes swollen and soft
and undergoes cavitations (Markson and Wells, 1982).
Gross lesions include flattening of cerebral gyri, hemorrhages, necrosis to
cavitations in the gray matter of the occipital and temporal regions (Fig.
1) and herniation of the cerebellum in some cases (Summers
et al., 1995). Interstitial and bullose emphysema are visualized in
the lung. In the histopathological analysis of cerebral cortex, the neuropil
exhibits spongiosis, neuronal necrosis, hemorrhages, perivascular edema and
vascular hyperplasia. Cavitations and accumulation of Gitter cells are seen
in grey matter. Interlobular interstitial and alveolar emphysema and mononuclear
cell infiltration can be detected in the lungs (Kul et
al., 2006). Brains of animals that survived for a longer period of time
have reduced sizes and feature areas almost totally devoid of cortex and sometimes
with small cysts. In these areas only a thin layer of the cortex or the meninges
cover the white substance (Summers et al., 1995).
|| Locally extensive cavitation (malacia) located in the cerebral
cortex, frontal lobe
The poliencephalomalacia is an entity related to multiple factors, which causes neurological changes in ruminants. The diagnosis of PEM is based on clinical signs, laboratory analysis and history of the herd management. Gray matter necrosis to cavitation in occipital and temporal regions are considered pathognomonic changes for PEM.
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