PRODUCTION ANIMALS

Neurological diseases of ruminant livestock in Australia. II: toxic disorders and nutritional deficiencies avj_793

247..253

JW Finnie,a* PA Windsorb and AE Kessellc

The second in this series of clinical reviews on neurological diseases in ruminant livestock in Australia examines toxic disorders associated with plant and microbial toxins as well as the neurological effects of vitamin and mineral deficiencies. The aim of these reviews is to assist in the surveillance of neurological diseases, especially the transmissible spongiform encephalopathies. Keywords Australia; livestock; neurological diseases; ruminants Abbreviations H&E, hematoxylin and eosin Aust Vet J 2011;89:247–253

doi: 10.1111/j.1751-0813.2011.00793.x

I

nvestigation of any disease that is suspected of involving the nervous system requires both a systematic neurological examination to determine the most probable neuroanatomical location of the lesions1 and knowledge of the most likely causes, to facilitate the diagnosis of endemic and emerging disorders. Toxic disorders Plant-associated toxins Many plant species in Australia, both native and introduced, contain substances that are harmful to livestock and still others harbour bacteria or fungi that elaborate injurious toxins. Plant poisonings are complex. With some plants, the toxicity is seasonal and dependent on the stage of growth or prevailing climatic conditions. Some contain low concentrations of toxin and signs are only produced when large quantities of the plant are rapidly consumed. Toxicity may be cumulative with others and the clinical effects from the date of initial exposure delayed. Some animals develop a tolerance to plant toxins or, under adverse conditions such as drought, begin to eat a plant they have previously avoided in preference to others.2 There are several seasonal phytogenous tremorgenic syndromes from which animals often recover when moved to new pastures.

Ryegrass staggers. Perennial ryegrass (Lolium perenne) staggers in sheep and cattle is caused by indolic lolitrems produced by the endophytic fungus Neotyphodium (Acremonium) lolii and, histologically, there may be a proximal cerebellar axonopathy with torpedo-like *Corresponding author. a SA Pathology, Institute of Medical and Veterinary Science and School of Animal and Veterinary Science, University of Adelaide, Adelaide, SA, Australia; john.finnie@ health.sa.gov.au b Faculty of Veterinary Science, University of Sydney, Sydney, NSW, Australia c Gribbles Veterinary Pathology, Adelaide, SA, and School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia

© 2011 The Authors Australian Veterinary Journal © 2011 Australian Veterinary Association

PRODUCTION ANIMALS

REVIEW

swelling of Purkinje cell axons. However, because the clinical signs are reversible, it is debatable whether this lesion is actually responsible for the neural dysfunction.3–6

Phalaris staggers. Some Phalaris spp., such as P. aquatica (tuberosa), contain dimethyltryptamine alkaloids that are monoamine oxidase inhibitors and interfere with the action of the neurotransmitter, serotonin. Grazing this plant may produce two neurological disorders. The first is an acute form in sheep, characterised by severe astrocytic oedema of the deep laminae of the cerebral cortex, resembling ammonia intoxication. There is also a more rapid and lethal form of Phalaris poisoning in sheep attributed to cardiotoxic agents. The second is a staggers syndrome in sheep, and occasionally cattle, which may be ameliorated by prior oral cobalt treatment and is sometimes delayed for months after ingestion. There is pathological evidence that this delayed form of the disease results in an induced storage product characterised by accumulation of a green-brown, lysosomallike, granular pigment in the neurons of the brainstem and spinal cord (Figure 1). When severe, there may even be greenish discolouration of affected grey matter. This pigment is not thought to be responsible for the neurological signs. However, there is also Wallerian degeneration in the long descending motor tracts of spinal cord and brainstem, which is a more probable cause. When affected sheep are disturbed, they become hyperexcitable and may exhibit generalised muscle tremors, stiff limb movements and hindquarter incoordination, which can sometimes progress to tetanic seizures. Sheep may appear to recover after removal from the pasture, but relapses frequently occur and many eventually die.7,8 Both L. perenne and P. aquatica are widely distributed in the temperate regions of Australia.5,6 Paspalum staggers. This condition, most frequently seen in cattle and occasionally sheep in New South Wales, Victoria and southwestern Western Australia, and known as nervous ergotism, is caused by tremorgenic paspalitrems produced by the fungus, Claviceps paspali, which parasitises Paspalum spp. A similar tremorgenic mycotoxicosis associated with heavy infestation of barley and wheat by Aspergillus clavatus has also been reported in cattle and sheep. Pathological features include neuronal degeneration in certain brainstem nuclei and the spinal cord, and sometimes Wallerian degeneration of the spinal cord.9,10 Induced neuronal storage disease. Ingestion of two plant species, Swainsona galegifolia (Darling pea), mainly in the inland areas south of the Tropic of Capricorn, and Trachyandra divaricata (branched onion weed), principally in south-west Western Australia, can result in induced storage disease in all grazing livestock. Swainsona spp. contain an indolizidine alkaloid, swainsonine, which is a potent inhibitor of lysosomal a-mannosidase, resulting in the intracellular

Australian Veterinary Journal Volume 89, No 7, July 2011

247

PRODUCTION ANIMALS

PRODUCTION ANIMALS

dental ingestion of cyanide-containing chemicals is possible, cyanide poisoning in ruminants is most commonly caused by the ingestion of rapidly growing cyanogenic plants. Although cyanogenic glucosides are found in a large number of Australian plant species, relatively few are implicated in livestock poisonings, because of their low palatability and low concentration of this substance. Cyanogenic glucosides are precursors of hydrogen cyanide and, when the plant is crushed, specific b-glucosidase enzymes usually resident in separate compartments of the plant come into contact with cyanogenic glucosides and accelerate the release of hydrogen cyanide. Cyanide poisoning most commonly occurs from ingestion of the various species of Sorghum cultivated for grain or grazing in the warmer parts of Australia.2,3,18,19 They also contain toxic quantities of nitrate. Other plants, such as Avena sp. (oats);2,3,5 Brachyachne sp. (native couch),2,3,5 Eremophila sp. (native fuschia)2,3,5 and Dysphania glomulifera (red crumbweed)20 in tropical Australia and Eucalyptus cladocalyx (sugar gum)21 in New South Wales and Victoria, may also cause cyanide poisoning. Figure 1. Ovine. Neuronal accumulation of granular pigmented material (arrowhead) in Phalaris staggers. (H&E; bar = 10 mm.)

accumulation of a mannose-containing oligosaccharide that induces a form of a-mannosidosis.11–13 The disease resembles the inherited (autosomal recessive) lysosomal storage disease of the same name in Angus and Murray Grey cattle,14 except that swainsonine also inhibits Golgi mannosidase II. In cattle, signs of toxicity appear mainly in young stock some weeks after spring rain and the consumption of plants. Animals exhibit loss of condition and neurological signs such as head shaking, hyperexcitability, irregular gait and incoordination. Removal from affected pasture in the early stages of disease may result in remission, otherwise animals eventually collapse and die. Sheep may simply become emaciated and die without neurological signs. There are usually no recognisable gross lesions. Histologically, neuronal perikarya are greatly distended and have a vacuolated, foamy appearance, because of removal during fixation and paraffin-embedding of the uncatabolised substrate (glycoprotein) that has accumulated in lysosomes. The axon hillock of neurons may also be hypertrophied to accommodate the stored material, forming a meganeurite. Aberrant dendritic spines may develop and eosinophilic axonal spheroids are common.11–13 The weir vine (Ipomoea calobra) in western Queensland also contains swainsonine and calystegines (nortropane alkaloids), which together induce phenotypic expression of three lysosomal storage diseases in sheep and cattle, namely a-mannosidosis (inhibition by swainsonine) and a-galactosidosis and b-glucosidosis (inhibition by calystegines).2,4,15 Calystegines in Solanum cinereum (Narrawa burr) may also be responsible for cerebellar degeneration in goats and sheep in New South Wales.16 Consumption of Trachyandra sp. can cause a severe neuromuscular disorder with marked lipofuscin storage (lipofuscinosis) in all central and peripheral neurons. The stored pigment sometimes imparts a rusty-brown colour to affected neural tissue. Clinical signs seem to be irreversible, but the connection between these effects and the storage disease is unresolved.17 As mentioned earlier, ingestion of Phalaris sp. may also induce a neuronal storage disease.5,6

Phytogenous cyanide toxicity. Cyanide poisoning is an important cause of morbidity in Australian ruminant livestock. Although acci-

248

Australian Veterinary Journal Volume 89, No 7, July 2011

Toxic levels of hydrogen cyanide can cause acute or more protracted neurological dysfunction. When large amounts are absorbed from the rumen into the bloodstream, death can occur rapidly after trembling, recumbency and terminal convulsions caused by rapid inhibition of intracellular respiratory enzymes. More chronic absorption also leads to inhibition of intracellular respiratory enzymes, causing histotoxic hypoxia and brain lesions, which manifest as selective neuronal necrosis and white matter oedema.2,3,18,19 Prolonged grazing of sorghums by cattle has been linked to ataxia, with diffuse Wallerian degeneration in lateral and ventral funiculi of the spinal cord, but whether cyanogenic compounds are the cause of this is still problematic.2,4 Similarly, sheep grazing sorghum may also show neurological signs, the lesion being an axonopathy with proximal spheroids in brainstem and ventral horn spinal cord neurons.22

Nitrate–nitrite poisoning. High nitrate levels in rapidly growing, immature oat crops (Avena sativa),2,3,5 ryegrass (Lolium spp.) pastures under certain conditions,23 Sorghum spp. (sorghum) and plants such as Amaranthus retroflexus (pigweed),2,3,5 Arctotheca calendula (capeweed),24 Silybum marianum (variegated thistle)2,3,5 and Salvia reflexa (mintweed)2,3,5 can produce muscle tremors, a staggering gait and terminal convulsions in ruminant livestock. Nitrate is reduced to nitrite in the rumen and, when it enters the circulation, haemoglobin is converted to methaemoglobin, leading to anaemic hypoxia. There are no macroscopic or microscopic lesions in the brain or other regions of the nervous system.2 Hepatotoxicity. When toxic substances, particularly ammonia, produced by the gut are not detoxified by the liver, hepatic damage leading to encephalopathy sometimes ensues, because of either congenital or acquired portosystemic vascular shunts or severe, diffuse acquired liver disease. The majority of cases in adult ruminants are the result of grazing plants containing pyrrolizidine alkaloids, particularly Heliotropium europaeum (common heliotrope, potato weed) and Echium plantagineum (Salvation Jane or Paterson’s curse), which are widely distributed over the mixed wheat–sheep areas of temperate Australia, but less frequently Senecio spp. (fireweed, ragwort) in temperate regions, Amsinckia sp. (yellow burr weed) in the eastern States, Crotalaria spp. (rattlepods) mainly in tropical and subtropical regions, and Cynoglossus spp., which are native to most States.2,25 Some neuro© 2011 The Authors Australian Veterinary Journal © 2011 Australian Veterinary Association

logical signs are also produced by mycotoxic hepatic damage from phomopsin produced by Phomopsis leptostromiformis on Lupinus plants (lupinosis)26 and sporidesmin produced by Pithomyces chartarum (facial eczema)2,4 on damp, dead ryegrass (L. perenne).27 Hepatopathy can result in an inability to excrete excess copper and results in chronic copper poisoning in sheep.28,29 Neurological manifestations of liver failure range from depression, listlessness and aimless wandering to mania and generalised convulsions. Microscopically, there may be spongy vacuolation of myelin (status spongiosis) in fibre tracts (see figure 1 in Finnie et al.1) and sometimes Alzheimer type II change in astrocytes, which appear markedly swollen with clear nuclei showing chromatin margination. The latter is more a feature of hepatic encephalopathy in horses than in ruminants.4,30 Cerebral status spongiosis is also produced as a secondary result of severe hepatic damage in cattle and sheep grazing Helichrysum blandowskianum (woolly everlasting daisy) in Victoria and South Australia.31

Urea poisoning. Damage to the brain from hyperammonaemia can also occur with urea poisoning because of inappropriate formulation of feed containing urea as a source for rumenal protein synthesis.5 Renal encephalopathy is an uncommon complication of uraemia in ruminants and is characterised by status spongiosis of the white matter, without Alzheimer type II astrocytosis.32 Corynetoxin poisoning. This condition is a severe and frequently fatal neurological disorder of sheep and cattle caused by the ingestion of several plant genera (Lolium, Polypogon and Agrostis) colonised by a nematode (Anguina agrostis) and a bacterium (Rathayibacter toxicus). Corynetoxin-producing R. toxicus is transported onto the host plants by nematode larvae and then ingested by grazing livestock. Corynetoxins are tunicaminyluracil antibiotics and their toxicity is related to specific and potent inhibition of protein glycosylation. Significant livestock losses result from exposure to parasitised annual ryegrass (L. rigidum) during summer grazing in the wheat–sheep zones of South Australia and Western Australia, where it is known as ‘annual ryegrass toxicity’, annual beard grass (P. monspeliensis) in flood-prone areas of the south-east of South Australia and blown grass (A. avenacea) on the Darling river floodplains of northern New South Wales, often termed ‘flood plain staggers’. Neuropathological lesions are not obvious, but perivascular plasma leakage in the cerebellar meninges is sometimes found.33 Neurological signs, which include muscle tremors, ophistotonus, convulsions, bruxism and nystagmus, may be evident within 1–2 weeks after introduction of livestock to toxic pastures, but can take up to 12 weeks. Removal of surviving stock from toxic pastures usually results in cessation of neurological signs after approximately 1 week.33

Less common plant intoxications. Other plants infrequently cause neurological disturbance but, when it occurs, can produce substantial morbidity and sometimes mortality. In some cases, cessation of consumption leads to recovery, while in others the neurological signs are progressive, resulting in permanent neurological deficits, sometimes blindness, and even death. Stypandraglauca (blindgrass) in the southwest of Western Australia contains the binaphthalene tetrol, stypandrol, which produces spongy degeneration of the brain (spongiform myelinopathy) in sheep and goats and Wallerian degeneration of optic © 2011 The Authors Australian Veterinary Journal © 2011 Australian Veterinary Association

nerves resulting in blindness.2,34,35 Tribulus terrestris (caltrop) in New South Wales is associated with a putative b-carboline alkaloid-induced disease in sheep. Asymmetrical hindlimb paresis (‘Coonabarabran staggers’) eventually progresses to quadriplegia and there is mild, but widely distributed, Wallerian degeneration of the spinal cord.36 Plants such as Gastrolobium and Oxylobium spp. in southern Western Australia, G. grandiflorum, which is widely distributed in tropical northern Australia, and Acacia georginae in north-west Queensland and the Northern Territory contain fluoroacetate. Ingestion by herbivores leads to failure of cellular respiration, with muscle tremors, incoordination,convulsions and mania.2,3 Palm-like plants of the cycad family (Cycas, Zamia, Macrozamia and Bowenia spp.) in the tropical north of Australia induce a distal axonopathy in the spinal cord with severe hindlimb ataxia (‘Zamia staggers’) in cattle.2,37 Demyelination of the spinal cord and caudal brainstem following ingestion of Xanthorrhea spp. (grasstree, yacca), occurring in all States, produces a distinctive type of incoordination, affected cattle lurching to one side, swinging laterally, and falling heavily to the ground (‘wamps’).2,38

PRODUCTION ANIMALS

PRODUCTION ANIMALS

Gait abnormalities, muscle tremors, paresis and paralysis, and recumbency are among the presenting signs in sheep following consumption of Romulea rosea (onion or Guildford grass) in Victoria and New South Wales, Echinopogon spp. (rough bearded grass) in New South Wales, Lamium amplexicaule (deadnettle) in New South Wales and Queensland, and Malva parviflora (marshmallow) and Stachys arvensis (staggerweed) in all States.2,39,40 A recent report suggests that R. rosea ataxia in sheep may be the result of depletion of cerebellar Purkinje cells.40 A staggers syndrome with quadraparesis has been reported with fenugreek (Trigonella foenum-graecum) consumption in Victoria and South Australia, acute cerebral oedema being found in rapidly developing cases and Wallerian degeneration of peripheral nerves when there is chronic duration.41 A convulsive syndrome is produced in sheep in northern Australia following consumption of Terminalia oblongata (yellow-wood)2,3 and ingestion of Pisum sativum (field pea) in Victoria and southern Queensland causes manic behaviour in cattle and sheep.2,42 Hoya australis (hoya, wax flower) may cause incoordination, muscle tremors, and clonic and tetanic spasms when grazed by cattle and sheep in inland Queensland43 and consumption of Chamaecytisus proliferus (tagasaste) by cattle in Western Australia is associated with a staggers syndrome and congenital leucoencephalopathy.2,44 Microbial toxins

Clostridium perfringens type D neurotoxicity. Clostridium perfringens type D is harboured by many sheep in the alimentary tract. In thriving lambs and calves, especially, that are grazing abundant, lush pasture or young cereal crops, large quantities of starch pass into the small intestine, which allows rapid proliferation of the clostridial organisms and a large amount of epsilon toxin is produced.45,46 Many lambs are found dead without premonitory signs or die after a few minutes of violent convulsive activity.45,46 Following intestinal absorption, high levels of circulating toxin accumulate preferentially in the brain (and kidney) and cause receptor-mediated cerebral microvascular endothelial damage (Figure 2). Disruption of the blood–brain barrier leads to a severe, diffuse vasogenic oedema and an acute or peracute clinical course to death (acute enterotoxaemia). There is also

Australian Veterinary Journal Volume 89, No 7, July 2011

249

PRODUCTION ANIMALS

PRODUCTION ANIMALS

Tetanus. In anaerobic wound conditions that may be produced by castration, docking, shearing or parturition, the potent neurotoxin, tetanospasmin, may be elaborated by Clostridium tetani.5,48 This toxin interferes with the release of the inhibitory transmitter, glycine, at presynaptic terminals, resulting in prolonged muscle contractions, which eventually involve the entire musculature. In cases of both botulism and tetanus, the respective toxins cause severe synaptic dysfunction, which can be fatal, but brains in routine histological sections appear normal.4 a

Algal and coccidial toxicity. Blue-green algae (cyanobacteria) proliferate in lakes and slow-flowing rivers during summer. The toxic principle (anatoxin-a) of the cyanobacterium, Anabaena sp., is neurotoxic, being a potent agonist at the nicotinic acetylcholine receptor, leading to muscle twitching, weakness, recumbency and rapid death. Anabaena sp. in Australia also contain a saxitoxin, a neurotoxin that acts as a selective sodium-channel blocker.2,3 A neurotoxin is also believed to be occasionally responsible for neurological signs, including tremors, nystagmus, opisthotonus and convulsions, in cattle with enteric coccidiosis and death may occur within a few days.49 Metallic poisons and drugs

b Figure 2. Ovine. Clostridium perfringens type D intoxication (a) Acute, showing severe endothelial damage (arrows) in the cerebellum; the capillary lining is markedly attenuated and electron-dense (electron micrograph). (b) Subacute, showing the bilateral, symmetrical necrosis (arrows) in the globus pallidus. (Courtesy of the Atlas of veterinary neuropathology, College of Veterinary Medicine, Cornell University.) Bar = 10 mm.

activation of glutamatergic and dopaminergic systems.45,46 With lower toxin levels, or in partially immune sheep, a focal, bilaterally symmetrical encephalomalacia (Figure 2) sometimes occurs in selectively vulnerable brain regions (frequently basal ganglia, internal capsule, thalamus and substantia nigra) after a more protracted clinical course.47 Focal, symmetrical encephalomalacia probably occurs in calves, although much less commonly, but not in goats.45,46

Botulism. Botulism is an ascending paralysis produced by ingestion of the preformed botulinum toxin (botulin) elaborated by Clostridium botulinum and is generally fatal in ruminants. The exotoxin acts at neuromuscular junctions, causing progressive flaccid muscle paralysis, affecting first the jaw and throat, then hindlimbs and, finally, forelimbs and the diaphragmatic and intercostal muscles. Eventually, animals become laterally recumbent and semi-comatose, but there is no loss of sensation. In cattle, lack of normal lingual muscle tone is a characteristic feature of advanced stages of botulism, although this also occurs in lead poisoning and snakebite.5,48 The common clinical sign in the latter is also an ascending paralysis, although the range of toxic effects depends on the species of snake involved.5,48

250

Australian Veterinary Journal Volume 89, No 7, July 2011

Lead and selenium toxicity. Lead is one of the most important livestock poisons, affecting particularly cattle, but also sheep and goats. Paint, sump oil, old batteries and pasture contamination are the usual sources. Affected animals are depressed and blind, with head pressing and an aimless, staggering gait; more acutely intoxicated animals show continuous seizures. Lesions are inconsistent, but there may be brain swelling at necropsy and, microscopically, there is early spongiosis. The cellular effects of lead are the result of its substitution for calcium in the ionic cellular pump mechanism, because calcium accumulates in lead-exposed cells. This triggers mitochondrial release of calcium, leading to apoptotic cell death. The importance of vascular injury in the pathogenesis is suggested by prominent capillary dilatation and endothelial proliferation with increased permeability, which may be responsible for ischaemic–hypoxic neuronal red cell change. Laminar cortical necrosis is often evident in severe cases.50–53 Overdosing with selenium or grazing seleniferous (seleniumaccumulator) plants can also produce neurological disturbance with visual impairment (‘blind staggers’) in sheep.54

Organophosphate, chlorinated hydrocarbon and halogenated salicylanide toxicity. Organophosphate poisoning presents as either an acute syndrome because of inactivation of acetylcholinesterase and parasympathetic overstimulation or a delayed paralytic disorder involving inhibition of neuronal esterase. The latter may present days or several weeks after exposure as ptyalism and ataxia, weakness, proprioceptive defects, and paralysis. It is associated with a distal axonopathy, manifesting as bilaterally symmetrical Wallerian degeneration in the caudal brainstem and spinal cord.2,3,55 Insecticides of the chlorinated hydrocarbon group (DDT, chlordane, lindane, dieldrin) are reversible acetylcholinesterase inhibitors. Clinical signs are related to stimulation of the central nervous system and are mainly neuromuscular and behavioural. Neuropathological © 2011 The Authors Australian Veterinary Journal © 2011 Australian Veterinary Association

PRODUCTION ANIMALS

PRODUCTION ANIMALS

changes following exposure are few, because recovery is often rapid and complete, but there may be patchy neuronal necrosis in the brainstem and cerebellum.3 Halogenated salicylanides are long-acting anthelmintics (closantel, rafoxanide) for sheep and goats and accidental overdosing causes a spongiform myelinopathy in the central and peripheral nervous systems. The neurotoxic mechanism has not been determined.3 Hexachlorophene, used as a topical antiseptic in neonates or as a fasciolicide, binds to myelin. It can also cause a spongiform myelinopathy in sheep. The myelin vacuolation is a form of cytotoxic oedema, in which the myelin remains stable. Hexachlorophene uncouples oxidative phosphorylation and reduces ATP synthesis in mitochondria; it also increases brain gamma-aminobutyric acid, the main inhibitory neurotransmitter.3,4 The rodenticide and vertebrate vermin control agent, 1080, contains fluoroacetate, a potent inhibitor of the tricarboxylic (Kreb’s) cycle enzymes, which paralyses cellular respiration, and neurological signs are described under poisonous plants.2,3

Figure 3. Bovine. Laminar cerebrocortical necrosis with numerous red neurons (arrows). Inset: resolving lesion with phagocytic microglia (gitter cells). (H&E; bar = 20 mm.)

Nutritional (vitamin and mineral) deficiencies Thiamine deficiency A deficiency of thiamine or a disturbance of its metabolism has been proposed as the cause of polioencephalomalacia (cerebrocortical necrosis) in cattle, sheep and goats and early cases may be thiamineresponsive. Thiamine (vitamin B1) is essential for several vital metabolic reactions, including linking the glycolytic pathway in the Kreb’s cycle, for reactions within the Kreb’s cycle and as a cofactor in the hexose monophosphate shunt. It is also required for maintenance of myelin membranes. This sometimes reversible deficiency can ultimately present as blindness, dullness, head pressing, muscle tremors, opisthotonus, recumbency, convulsions, coma and death. At necropsy, there is usually brain swelling, sometimes with herniation of the medulla and cerebellum into the foramen magnum. In more advanced cases, there may be laminar pallor of the cerebral cortex, which sometimes shows autofluorescence under ultraviolet light, because of mitochondrial derivatives. These macroscopic cortical features correspond microscopically to deep laminar or pseudolaminar necrosis with neuronal red cell change (eosinophilic neurons, ischaemic neuronal necrosis) (Figure 3), especially in the distribution of the middle cerebral artery. Less commonly, there may be bilaterally symmetrical degeneration of periventricular nuclei, particularly the caudal colliculus.4,6 This hypovitaminosis in sheep and cattle is frequently associated with intraruminal thiaminase activity, either from a high carbohydrate substrate-induced overgrowth of thiaminase-producing bacteria (Clostridium sporogenes and C. thiaminolyticum; Bacillus aneurolyticum) or may be associated with thiaminase in ingested plants such as bracken fern (Pteridium sp.), nardoo (Marsilea drummondi), mulga or rock fern (Cheilanthes seeberi) and horsetail (Equisetum sp.). Ingestion of high levels of dietary sulfur, which is thiaminolytic, may also produce this cerebrocortical lesion in cattle.56–62 Salt poisoning Sodium ion toxicosis (salt poisoning) produces a similar cerebrocortical lesion to that of thiamine deficiency in cattle and sheep. Rumi© 2011 The Authors Australian Veterinary Journal © 2011 Australian Veterinary Association

nants can tolerate relatively high salt levels in drinking water but, when salt deficient animals consume large quantities of salt in a highly palatable ration form, severe osmotic neurological disturbance results in brain swelling and death. Cerebral oedema is caused by a biphasic osmotic correction to increased salt levels in the brain and may lead to pseudolaminar cerebral cortical necrosis.63,64 Vitamin A deficiency Vitamin A deficiency in growing cattle may be primary or secondary. Primary hypovitaminosis A occurs most commonly from a lack of green feed during periods of drought or in feedlots, whereas secondary deficiency may occur with a combination of chronic hepatic and intestinal disease, because the liver is the principal storage site and conversion of carotene to vitamin A occurs in the alimentary tract. The fundamental lesion is asynchrony between development of the central nervous system and that of its bony encasement. The lack of sufficient vitamin A for osteoclasts causes failure of remodelling, with excess bone being produced where resorption should be taking place. At necropsy, compression of the brain combined with herniation of the cerebellar vermis is often observed. Increased intracranial pressure results in convulsive seizures and stenosis of the optic foramen causes compression of optic nerves, severe Wallerian degeneration and blindness. Similarly, compression of spinal nerves may produce paralysis. Hypersecretion of cerebrospinal fluid and impeded absorption from dural thickening can also induce hydrocephalus.4,65 Copper deficiency ‘Swayback’ and ‘enzootic ataxia’ occur in sheep and goats in all States as a result of copper deficiency. The role of copper in the developing nervous system is unclear, but inadequate levels impede cellular respiration, leading to energy deprivation. Copper deficiency may be primary and absolute, or secondary to impaired gut absorption, largely because of the presence of antagonists such as molybdenum. It is essentially a motor disturbance, evidenced by staggering, ataxia and, eventually, recumbency. Affected animals may be blind. Lambs with

Australian Veterinary Journal Volume 89, No 7, July 2011

251

PRODUCTION ANIMALS

PRODUCTION ANIMALS the congenital form show severe and bilaterally symmetrical cerebral white matter loss, which is probably the result of defective myelin formation and demyelination that leads to softening and finally cavitation. The delayed form is manifest weeks to months postnatally and is characterised by extensive Wallerian (neuroaxonal) degeneration in the spinal cord (Figure 4), predominantly in the dorsolateral and ventromedial tracts, consistent with a distal axonopathy. Additional neuronal degeneration in certain brainstem nuclei and spinal motor neurons may also occur. The myelin is probably abnormal and unstable. In goat kids, copper deficiency is expressed mainly as the delayed form, with an emphasis on cerebellar degeneration. Here there is necrosis and ectopia of Purkinje cells, depletion of the internal granular layer neurons, together with Wallerian degeneration in folite white matter, spinal nerve roots and peripheral nerves.66–68

Calcium deficiency Hypocalcaemia causes paresis in ruminants, reflecting its role in controlling acetylcholine release and gating neuromuscular junction signal propagation. This syndrome is also found in feed-deprived sheep consuming high-oxalate-containing pastures.5 Magnesium deficiency. Ruminants are especially sensitive to magnesium deficiency, with either low dietary magnesium or high potassium in lush green pasture inhibiting rumenal magnesium absorption. This leads to abnormal neuromuscular function, including spasticity, convulsions, tremor and tetany. There are no visible lesions in calcium or magnesium deficiency.5 References

a

b Figure 4. Ovine spinal cord. (a) Several digestion chambers containing macrophages (arrows) shown in longitudinal section (immunostaining for myelin basic protein). (b) Ionised calcium binding adaptor molecule 1 (Iba1)-expressing macrophage in a digestion chamber (arrow) with similarly immunostained microglial processes enveloping, and external to, the myelin ellipsoids. Iba1 is specifically expressed in macrophages/ microglia and upregulated during activation of these cells. Bar = 10 mm.

252

Australian Veterinary Journal Volume 89, No 7, July 2011

1. Finnie JW, Windsor PA, Kessell AE. Neurological diseases of ruminant livestock in Australia. I: general neurological examination, necropsy procedures and neurological manifestations of systemic disease, trauma and neoplasia. Aust Vet J 2011;89:243–246. 2. Everist SL. Poisonous plants of Australia. Angus and Robertson, Sydney, 1974:10–14. 3. McKenzie RA. Toxicology for Australian veterinarians (electronic resource). Ashgrove, Queensland, 2002;1–14, 18–28, 47–68, 74–88, 110–116, 130–147, 249– 250, 270, 272–291, 293–298, 300–303, 304–306. 4. Seawright AA. Chemical and plant poisons. Animal health in Australia. Vol. 2, 2nd edn. Bureau of Rural Resources, Department of Primary Industries and Energy, Commonwealth of Australia, 1989;14–16, 42–45, 54–57, 82–86, 99–101, 127–130, 149–150, 262–269, 250, 331–332. 5. Maxie MG, Youssef S. Nervous system. In: Maxie MG, editor. Jubb, Kennedy and Palmer’s pathology of domestic animals. Vol. 1, 5th edn. Elsevier, London, 2007;331, 347–348, 361, 364, 368, 370–371, 386–388. 6. Hungerford TG. Diseases of livestock. 9th edn. McGraw-Hill, New York, 1990;41– 44, 75–79, 163, 307–309, 313–317, 332–337, 339–343, 1567–1570, 1624–1689. 7. Sullivan ND. Neuropathology and pathogenesis in toxic injury to the nervous system. Aust Soc Vet Pathol Annu Conf Proc 2003;12–20. 8. Bourke CA, Rendell D, Colegate SM. Clinical observations and differentiation of the peracute Phalaris aquatica poisoning syndrome in sheep known as ‘polioencephalomalacia-like sudden death’. Aust Vet J 2003;81:698–700. 9. Bourke CA, Carrigan MJ, Dixon RJ. The pathogenesis of the nervous syndrome of Phalaris aquatica toxicity in sheep. Aust Vet J 1990;67:356–358. 10. McKenzie RA, Kelly MA, Shivas RG et al. Aspergillus clavatus tremorgenic mycotoxicosis in cattle fed sprouted grains. Aust Vet J 2004;82:635–641. 11. Ross AD, Morice G, Masters I. Mouldy feed neuropathy in feedlot sheep. Aust Soc Vet Pathol Annu Conf Proc 2003;33–34. 12. Huxtable CR, Dorling PR. Poisoning of livestock by Swainsonia spp.: current status. Aust Vet J 1982;59:50–53. 13. Huxtable CR, Dorling PR. Swainsonine-induced mannosidosis. Am J Pathol 1982;107:124–126. 14. Jolly RD, Walkley SU. Lysosomal storage diseases of animals: An essay in comparative pathology. Vet Pathol 1997;34:527–548. 15. Molyneux RJ, McKenzie RA, O’Sullivan BM, Elbein AD. Identification of the glucosidase inhibitors swainsonine and calystegine B2 in weir vine (Ipomoea sp. Q6 (aff. calobra) and correlation with toxicity. J Nat Prod 1995;58:878–886. 16. Bourke CA. Cerebellar degeneration in goats grazing Solanum cinereum (Narrawa burr). Aust Vet J 1997;75:363–365. 17. Huxtable CR, Chapman HM, Main DC et al. Neurological disease and lipofuscinosis in horses and sheep grazing Trachyandra divaricata (branched onion weed) in south Western Australia. Aust Vet J 1987;64:105–108. 18. McKenzie RA, McMicking LI. Ataxia and urinary incontinence in cattle grazing sorghum. Aust Vet J 1977;53:496–497. 19. Soto-Blanco B, Gorniak SL, Kimura ET. Physiopathological effects of the administration of chronic cyanide to growing goats: a model for ingestion of cyanogenic plants. Vet Res Commun 2001;25:379–389. 20. McKenzie RA, Burren BG, Noble JW, Thomas MB. Cyanide poisoning in cattle from Dysphania glomulifera (red crumbweed): using the internet for rapid identification and diagnostic advice. Aust Vet J 2007;85:505–509.

© 2011 The Authors Australian Veterinary Journal © 2011 Australian Veterinary Association

21. Webber JJ, Roycroft CR, Callinan JD. Cyanide poisoning of goats from sugar gums (Eucalyptus cladocalyx). Aust Vet J 1985;62:28. 22. Bradley GA, Metcalf HC, Reggiardo C et al. Neuroaxonal degeneration in sheep grazing Sorghum pastures. J Vet Diagn Invest 1995;7:229–236. 23. Nicholls TJ, Miles EJ. Nitrate/nitrite poisoning of cattle on ryegrass pasture. Aust Vet J 1980;56:95–96. 24. Fairnie JJ. Nitrite poisoning in sheep due to capeweed (Arctotheca calendula). Aust Vet J 1969;45:78–79. 25. Peterson JE. Plant poisoning research: pyrrolizidine alkaloids. Univ Sydney Post-Grad Cttee Vet Sci Proc 1987;103:93–110. 26. Allen JG, Nottle FK. Spongy transformation of the brain in sheep with lupinosis. Vet Rec 1979;104:31–33. 27. Thompson KG, Lake DE, Cordes DO. Hepatic encephalopathy associated with chronic facial eczema. NZ Vet J 1979;27:221–223. 28. Howell JM, Blakemore WF, Gopinath C, Hall GA, Parker JH. Chronic copper poisoning and changes in the central nervous system of sheep. Acta Neuropathol 1974;29:9–24. 29. Morgan KT. Chronic copper toxicity of sheep: an ultrastructural study of spongiform leucoencephalopathy. Res Vet Sci 1973;15:88–95. 30. Hooper PT. Spongy degeneration in the central nervous system of domestic animals. I: Morphology:. III: Occurrence and pathogenesis hepatocerebral disease caused by hyperammonaemia. Acta Neuropathol 1975;31:325–334, 343–351. 31. McAuliffe OR, White WE. ‘Woolly everlasting daisy’ (Helichrysum blandowskianum) toxicity in cattle and sheep. Aust Vet J 1976;52:366–368. 32. Summers BA, Smith CA. Renal encephalopathy in a cow. Cornell Vet 1985;75:524–530. 33. Finnie JW. Review of corynetoxins poisoning of livestock: a neurological disorder produced by a nematode-bacterium complex. Aust Vet J 2006;84:271–277. 34. Huxtable CR, Dorling PR, Slatter DH. Myelin oedema, optic neuropathy and retinopathy in experimental Stypandra imbricate toxicosis. Neuropathol Appl Neurobiol 1980;6:221–232. 35. Main DC, Slatter DH, Huxtable CR, Constable IC, Dorling PR. Stypandra imbricata (‘blindgrass’) toxicosis in goats and sheep: clinical and pathologic findings in 4 field cases. Aust Vet J 1981;57:132–135. 36. Bourke CA. Abnormal turning behaviour, GABAergic inhibition and the degeneration of astrocytes in ovine Tribulus terrestris motor neuron disease. Aust Vet J 2006;84:53–58. 37. Hooper PT, Best SM, Campbell A. Axonal dystrophy in the spinal cords of cattle consuming the cycad palm, Cycas media. Aust Vet J 1974;50:146–149. 38. Bourke CA. The clinical differentiation of nervous and muscular locomotor disorders of sheep in Australia. Aust Vet J 1995;72:228–234. 39. Philbey AW, Hawker AM, Evers JV. A neurological locomotor disorder in sheep grazing Stachys arvensis. Aust Vet J 2001;79:427–430. 40. Bourke CA, Bunker EC, Reece RL, Whittaker SJ. Cerebellar ataxia in sheep grazing pastures infested with Romulea rosea (onion grass or Guildford grass). Aust Vet J 2008;86:354–356. 41. Bourke CA. Are ovine fenugreek (Trigonella foenum-graecum) staggers and kangaroo gait of lactating ewes two clinically and pathologically similar nervous disorders? Aust Vet J 2009;87:99–101. 42. Reardon CR, McKenzie RA. Pea mania: deranged behaviour in cattle grazing a pea crop. Aust Vet J 2002;80:16–19. 43. Legg J, White CT. Hoya australis: a plant poisonous to stock. Aust Vet J 1939;15:34–36. 44. Forshaw D. Congenital leucodystrophy in calves linked to dams grazing tagasaste (Chamaecytisus palmensis). Vet Pathol Rep 1999;53:24–25.

© 2011 The Authors Australian Veterinary Journal © 2011 Australian Veterinary Association

45. Finnie JW. Pathogenesis of brain lesions produced in sheep by Clostridium perfringens type D epsilon toxin: a review. Aust Vet J 2003;81:219–221. 46. Finnie JW. Neurological disorders produced by Clostridium perfringens type D epsilon toxin. Anaerobe 2004;10:145–150. 47. Hartley WJ. A focal symmetrical encephalomalacia of lambs. NZ Vet J 1956;4:129–135. 48. Windsor PA. Pathology of the neuromuscular system of cattle: A review. Univ Sydney Post-Grad Cttee Vet Sci Proc 1987;97:319–340. 49. Jubb TF. Nervous disease associated with coccidiosis in young cattle. Aust Vet J 1988;65:353–354. 50. Fahy VA. Heavy metal toxicity, with reference to industrial development: Lead poisoning. Univ Sydney Post-Grad Cttee Vet Sci Proc 1987;103:319–325. 51. Christian RG, Tryphonas L. Lead poisoning in cattle: brain lesions and hematologic changes. Am J Vet Res 1971;32:203–215. 52. Lemos RA, Driemeier D, Guimaraes EB et al. Lead poisoning in cattle grazing pasture contaminated by industrial waste. Vet Hum Toxicol 2004;46:326–328. 53. Wells GAH, Howell JMcC, Gopinath C. Experimental lead encephalopathy of calves: histological observations on the nature and distribution of the lesions. Neuropathol Appl Neurobiol 1976;2:175–190. 54. Cooper BS. Sheep toxicoses from selenium supplementation. Univ Sydney Post-Grad Cttee Vet Sci Proc 1987;103:175–186. 55. Coppock RW, Mostrom MS, Khan AA, Stair EL. A review of nonpesticide esterinduced neurotoxicity in cattle. Vet Hum Toxicol 1995;37:576–579. 56. Evans WC, Evans IA, Humphreys DJ et al. Induction of thiamine deficiency in sheep, with lesions similar to those of cerebrocortical necrosis. J Comp Pathol 1975;85:253–267. 57. Pritchard D, Eggleston GW, Macadam JF. Nardoo fern and polioencephalomalacia. Aust Vet J 1978;54:204–205. 58. Gould CH. Polioencephalomalacia. J Anim Sci 1998;76:309–314. 59. Morgan KT. An ultrastructural study of ovine polio-encephalomalacia. J Pathol 1973;110:123–130. 60. Markson LM, Wells GA. Evaluation of autofluorescence as an aid to diagnosis of cerebrocortical necrosis. Vet Rec 1982;111:338–340. 61. Haydock D. Sulphur-induced polioencephalomalacia in a herd of rotationally grazed beef cattle. Can Vet J 2003;44:828–829. 62. McKenzie RA, Carmichael AM, Schibrowski ML et al. Sulfur-associated polioencephalomalacia in cattle grazing plants in the Family Brassicacea. Aust Vet J 2009; 87:27–32. 63. Scarratt WK, Collins TJ, Sponenberg DP. Water deprivation-sodium chloride intoxication in a group of feeder lambs. J Am Vet Med Assoc 1985;186:977– 978. 64. Trueman KF, Clague DC. Sodium chloride poisoning in cattle. Aust Vet J 1978;54:89–91. 65. Hill BD, Holroyd RG, Sullivan M. Clinical and pathological findings associated with congenital hypovitaminosis A in extensively grazed beef cattle. Aust Vet J 2009;87:94–98. 66. Howell JM, Davison AN, Oxberry J. Observations on the lesions in the white matter of the spinal cord of swayback sheep. Acta Neuropathol 1969;21:33– 41. 67. Seaman JJ, Hartley WJ. Congenital copper deficiency in goats. Aust Vet J 1981;57:355–356. 68. Wouda W, Borst GH, Gruys E. Delayed swayback in goat kids: a study of 23 cases. Vet Q 1986;8:45–56.

PRODUCTION ANIMALS

PRODUCTION ANIMALS

(Accepted for publication 12 August 2010)

Australian Veterinary Journal Volume 89, No 7, July 2011

253