Nutritional and Metabolic Diseases

Polioencephalomalacia

Also known as cerebrocortical necrosis, this nutritional/ metabolic disease primarily affects ruminants, including goats. The disease in goats is increasingly recognized under intensive management conditions when goats are fed more grain concentrate feed to encourage accelerated growth or increased production.

Etiology and Pathogenesis

Strictly speaking, PEM is a descriptive term for a softening of the gray matter of the cerebral cortex, also referred to as cortical necrosis. The term does not inherently ascribe a particular etiologic basis for the occurrence of such a lesion. Yet, over the years, the term has become closely linked in veterinary medicine to a specific syndrome of ruminants believed to be caused by disturbances of thia­mine (vitamin B₁) metabolism, which occurs most com­monly in feedlot cattle and other ruminants on high-concentrate rations. However, there is growing recog­nition that other conditions besides disturbance of thia­mine metabolism can otherwise cause the same lesion of PEM. These conditions include sulfur toxicosis as well as lead poisoning and salt poisoning/water deprivation. The characteristic microscopic lesions of PEM have also been reported in a solitary case of closantel overdosage in a goat (Sakhaee and Derakhshanfar 2010).

There are several reasons for the traditional association of PEM with thiamine. In ruminants, thiamine is produced by the activity of rumen bacteria and dietary sources of the vitamin are not required under normal conditions. PEM is most commonly seen in cattle in feedlots on high-grain rations. It is documented that when the pH of the rumen is reduced, as occurs with the feeding of grain rations, rumen bacteria that produce thiamine are reduced in number, while other bacteria that produce thiaminase, an enzyme that degrades thiamine, are increased.

But perhaps the most compelling argument for the belief that thiamine plays a central role in the pathogenesis of PEM has been that administration of thiamine to clinical cases, particularly early in the course of disease, frequently results in the recovery of affected animals. Nevertheless, current thinking suggests that the positive therapeutic effect of thiamine does not prove that thiamine deficiency or inhibition is the underlying etiologic basis for PEM. Rather, it is now thought that thiamine may improve energy metabolism in the impaired brain regardless of the inciting cause of the PEM (Niles et al. 2002).

Thiamine has important physiologic functions. It is part of the coenzyme TPP, which plays numerous roles in carbo­hydrate and amino acid metabolism. It participates in the tricarboxylic acid cycle as a cofactor in the oxidative decar­boxylation of alpha ketoglutarate to succinate and in the conversion of pyruvate to acetyl CoA. In addition, as a coen­zyme of transketolase, it participates in the pentose phos­phate pathway to create D-glyceraldehyde-3-phosphate.

The pathophysiology of the PEM lesion is not fully understood. It is believed to result from intracellular edema associated with a dysfunction of the adenosine triphos­phate (ATP)-dependent sodium potassium pump (Cebra and Cebra 2004). Failure of the pump results in sodium accumulation within cells and a resulting net influx of water, leading to cell swelling and death. Most neuronal ATP is generated through glycolysis via the pentose phos­phate pathway; transketolase is the rate-limiting enzyme in the pathway and TPP serves as an important cofactor to transketolase.

Another development that has challenged the central role of thiamine in the pathogenesis of PEM is the emer­gence of sulfur toxicity as a demonstrable cause of PEM. It has been documented in situations such as cattle feedlots, where cases were historically attributed to thiamine defi­ciency. Elemental sulfur, as well as inorganic and organic sulfur compounds, may be present in water and a wide range of animal feeds, including forages, concentrates, and molasses, and overall dietary intake may present poten­tially toxic levels of sulfur. The rumen contains a range of bacteria that metabolize sulfur in different ways. So-called assimilatory bacteria reduce sulfate for their own meta­bolic utilization and to make sulfur-containing amino acids. Dissimilatory bacteria also use sulfur for their own metabolic needs, but they produce excess amounts of sulfide, which accumulate in the rumen. A third group of bacteria contain cysteine desulfhydrase and liberate addi­tional sulfide by enzymatic reactions with sulfur-containing proteins (Gould 1998).

It is known that reductions in rumen pH, as occur in feedlots in association with concentrate feeding, favor the accumulation of hydrogen sulfide (H₂S) in the rumen gas cap, where it can readily diffuse into the portal blood­stream. If absorbed in excessive amounts, it may override the capacity for hepatic detoxification. In addition, if pre­sent in high concentration in the rumen gas cap, eructated H2S may be inhaled into the lungs and pass directly into the circulation across the pulmonary membranes.

H₂S has a high affinity for brain tissue because of its high lipid content, and therefore may exert its toxic effects most dramatically in the brain, leading to PEM by mechanisms not yet fully elucidated. The toxic effects of H2S gas on the respiratory tract are well known, as the inhalation of H2S from manure pits leads to severe pulmonary edema and has been responsible for the deaths of livestock and humans. While it is known that high-sulfur diets can lower ruminal thiamine production, the pathophysiology of sulfur-related PEM does not necessarily involve thiamine deficiency. In reports of clinical cases of PEM in feedlot steers, rumen H₂S levels were elevated, while blood thia­mine levels remained in the normal range (McAllister et al. 1997). Current perspectives on PEM and its causes, with an emphasis on sulfur toxicity, have been reviewed (Gould 1998, 2000; Niles et al. 2002; Lutnicki et al. 2014).

The existence of a relationship between sulfur and thia­mine in the evolution of PEM has been studied experimen­tally in beef cattle (Amat et al. 2013). Results indicated that high dietary sulfur intake may increase the metabolic demand for TPP, and that animals incapable of maintain­ing requisite levels of brain TPP are at high risk to develop PEM. TPP is a critical cofactor in several key energy metab­olism pathways and alterations in TPP synthesis or supply are often associated with neurologic disorders in humans.

Epidemiology

Information is sparse on the worldwide incidence of caprine PEM. Currently the disease is presumed to occur only sporadically in goats. Nevertheless, it has been reported to be the most commonly seen nervous disease of goats in New Zealand (McSporran 1988).

The pattern of disease in goats is not as well established as in cattle or sheep, but, as in those species, dietary and management factors that may alter normal rumen flora appear to play a key role. Sudden changes in diet, excessive feeding of concentrates, use of horse feeds high in molas­ses, feeding of moldy hay, development of rumen acidosis, dietary stress of weaning, and overdosing of amprolium have all been associated with cases of caprine PEM. Given that it is now well documented in cattle and sheep that excess consumption of sulfur in the water and feed can also produce PEM, it is reasonable to assume that this also can occur in goats. However, at the time of this writing, no field cases have been documented in goats with sulfur toxicity as the confirmed etiology.

In North America, an increased occurrence in winter has been noted, when roughage quality and availability are low and grain feeding is increased (Smith 1979). It is known that sulfur and sulfates can be found in high quantities in drinking water, notably in the Plains and intermountain regions of the United States and Canada, and this could contribute to the development of PEM. In India, cases increased between August and December when lush pas­ture was available (Tanwar 1987). In South Africa, an out­break was associated with concentrate supplementation during winter grazing (Newsholme and O’Neill 1985).

Poor growth rate has been associated with subclinical thiamine deficiency in lambs. One study demonstrated that normal goats in herds where clinical PEM occurred had more thiaminase activity in feces than did normal goats in herds with no history of the disease. This suggests that subclinical thiamine deficiency may occur in goats as well (Thomas et al.

Clinical Findings

All goats are susceptible to PEM, but most cases involve weanlings and young adults. The history frequently includes a sudden change in feed, increases in concentrate feeding, difficulties in weaning, or a recent bout of diges­tive disease. The initial presentation is variable, with some animals showing a prodromal period of depression, ano­rexia, and/or diarrhea, with gradual expression of neuro­logic abnormalities over a period of one to seven days. In most cases, however, the presentation is one of acute neu­rologic dysfunction. Early neurologic signs include excita­bility, elevation of the head or opisthotonos while standing, staring off into space (stargazing), aimless wandering, cir­cling, ataxia, muscle tremors, and apparent blindness.

As the disease progresses, dorsomedial strabismus, nys­tagmus, lack of a menace response, extensor rigidity, odon­toprisis, recumbency with opisthotonos, and convulsions are observed. Fever is not seen except in association with convulsions. The pupillary reflexes are variable, depending on the degree of cerebral edema. Rumen contractions are present in uncomplicated PEM, but they may be absent if the condition was precipitated by a severe rumen acidosis. If there is no therapeutic intervention, goats usually die between 24 and 72 hours after onset of clinical signs.

Clinical Pathology and Necropsy

Goats with PEM show little or no change in the CSF except for a slight mononuclear pleocytosis. While CSF pressure would be expected to increase, normal CSF pressures are poorly documented in the goat. In one reported case of PEM, the CSF pressure was 220 mm water (deLahunta 1977).

Measurement of transketolase activity of red blood cells offers an indirect measurement of thiamine levels. In one study, the mean transketolase activity in nine normal goats measured as μmol pentose/hour/10⁹ red blood cells was 0.782, with a range of 0.125-2.90, compared with levels of 0.099 and 0.068 in two clinically affected goats (Smith 1979). In another study, mean transketolase activity in normal goats was reported as 35 ± 5 IU/L, compared with 18 ± 2 in affected goats (Thomas et al. 1987). To have the transketo­lase assay performed, heparinized blood should be centri­fuged for 10 minutes at 3000 g, the plasma discarded, and the red cells frozen at -20 °C (-4 °F) for shipment to the laboratory.

Thiaminase activity can be measured in feces of live ani­mals or rumen content at necropsy. Fresh samples should be submitted frozen to the laboratory and at least 60 g of rumen content provided. In normal goat feces, thiaminase activity has been measured as 0.2 ± 0.1 mU/g, and 0.8 ± 0.3 in clinically affected goats. In normal goats no rumen fluid thiaminase activity was detected, while a mean activity of 0.5 ± 0.3 mU/mL was measured in clini­cally affected goats (Thomas et al. 1987).

The calculated normal reference range for blood thia­mine levels in goats has been reported as 66-178 nmol/L, but the diagnostic value of such measurements in clinically affected goats remains uncertain. At necropsy, decreased tissue thiamine levels support the diagnosis of PEM (Rammell and Hill 1988). Liver and brain samples should be submitted frozen. Mean liver thiamine levels in normal goats have been reported as 1.6 ± 0.3 μg∕g wet weight, and 0.3 ± 0.4 in affected goats. In brain, the mean for normal goats was 0.7 ± 0.1 and 0.3 ± 0.1 in affected goats (Thomas et al. 1987).

Confirming the presence of high concentrations of H₂S in the rumen gas cap can support the diagnosis of sulfur toxicosis as the underlying cause of PEM. A technique for sampling the rumen gas cap through the left paralumbar fossa using a commercially available H₂S detection tube has been described (Gould et al. 1997). Normal and diag­nostic values for the goat have not been specifically reported, but in cattle, steers on a high-carbohydrate diet supplemented with sodium sulfate developed PEM and had rumen H2S gas concentrations 40-60 times higher than control steers on the same diet without sodium sulfate supplementation. The H2S concentration in the supple­mented steers was 4850 ppm by the fifth day of feeding, while the concentration in non-supplemented steers never exceeded 75 ppm during the experimental trial (Gould et al. 1997). It is recommended that in field cases the analy­sis be performed when possible on healthy herd mates of the clinically affected animals, because sick animals that are off feed quickly revert to lowered concentrations of H₂S in the rumen and may therefore give false-negative results. If quantitative testing cannot be performed, the breath of affected animals should be checked during eructation for the characteristic “rotten egg” odor of H₂S, which can give a qualitative indication that sulfur toxicity may be involved.

Gross necropsy findings are limited to the brain. In the most severe cases, the cerebrum is soft and edematous, with a grayish yellow or yellow discoloration. The cerebral gyri appear flattened from pressure and the cerebellum may be partially herniated through the foramen magnum. In less severe cases, examination of the cerebrum in dark­ness using an ultraviolet lamp (black light) may demon­strate areas of fluorescence in the cortex associated with cerebrocortical necrosis. Histologically, a laminar necrosis is confirmed in affected gyri with evidence of separation of the gray and white matter, and obvious degeneration of neurons with perineuronal vacuolation.

In cases where grain engorgement is a predisposing fac­tor, evidence of rumenitis and other sequelae of lactic aci­dosis may be observed.

Diagnosis

Early signs of depression or altered mentation and diar­rhea are consistent with enterotoxemia caused by Cl. per- fringens or pregnancy toxemia. The former disease might respond favorably to antitoxin administration; the latter occurs in pregnant does, usually with positive urine ketones. The combination of blindness, opisthotonos, extensor rigidity, nystagmus, and strabismus is strongly suggestive of PEM in goats. These signs, however, may occur successively, simultaneously, or not at all, and defini­tive diagnosis is not always easy. The differential diagnosis for acute, central blindness is given in Chapter 6.

Opisthotonos and extensor rigidity are also characteristic of tetanus and goats with advanced PEM can easily be mis­taken for tetanus cases. When circling or other unilateral signs are seen, listeriosis, brain abscesses, ear infections, cerebral nematodiasis, and CAE must be considered. Listeriosis is associated with changes in the CSF and the other diseases are more slowly progressive. Terminal cases of PEM are often convulsive and therefore meningitis, rabies, pseudorabies, and a variety of toxicoses must be considered in the differential diagnosis. As discussed above, lead poisoning and salt poisoning can produce the brain lesion of PEM and may therefore also produce simi­lar clinical signs.

While laboratory tests can support the diagnosis of PEM, the critical nature of the disease demands swift interven­tion by the practitioner, usually before such laboratory results are ever available. In practice, PEM is most often diagnosed by a response to therapy with thiamine. In goats, evidence of therapeutic response may be seen as soon as two hours after treatment.

Treatment

Despite questions concerning the role of thiamine metabo­lism in the pathogenesis of PEM, administration of thia­mine remains the treatment of choice (Niles et al. 2002). Response is variable, depending mostly on the severity of the disease at the time treatment is initiated. The dose is 10 mg/kg bw, repeated every 6 hours for 24 hours. The ini­tial dose is usually given IV, and subsequent doses can be given IV, IM, or SC. However, there have been anecdotal reports of deaths in goats following IV administration, so if the IV route is used the drug should be delivered slowly, or the SC or IM route used instead. Thiamine hydrochloride is most frequently used. If only multiple B vitamins are avail­able, be sure that they are dosed according to the thiamine content. In early or mild cases, complete cure frequently occurs. In advanced cases, partial cures may occur, with permanent residual blindness or abnormal mentation. Severely affected goats may die despite therapy. In other species, IV hyperosmotic mannitol at a dose of 1.5 g/kg bw in a 20% solution and parenteral dexamethasone at 1-2 mg/ kg bw have been used in severe cases to reduce cerebral edema. The diuretic furosemide has also been used empiri­cally for that purpose at a dose of 1 mg/kg bw IV. Diazepam at 0.5-1.5 mg/kg or other anticonvulsants may be required when seizures occur.

In addition to thiamine therapy and the management of cerebral edema, any underlying problems that may have predisposed to PEM, such as grain engorgement, should be identified and treated, as should sequelae such as dehydra­tion and metabolic acidosis.

Control

A careful history is required to identify specific predispos­ing factors in each affected herd. Common control recom­mendations include an increase in roughage feeding with a concomitant decrease in concentrate feeding, and avoid­ance of moldy feeds and those containing large amounts of molasses, such as horse feeds. When weanlings are involved, weaning procedures should be reviewed to ensure that kids obtain adequate roughage before weaning to promote normal rumen development and proper rumen flora. In problem herds, supplementation of the grain ration with thiamine mononitrate or brewer's yeast may be indicated.

New information on sulfur toxicosis as a cause of PEM indicates that the total sulfur content of the ration, includ­ing the water supply, should be calculated and then reduced if it exceeds requirements. Levels of dietary sulfur able to produce toxicity in goats are not reported. In beef cattle, sulfur content of the total ration is recommended to be between 1500 and 2000 ppm (0.15-0.20% on a dry matter basis) and, to avoid toxicity, should not exceed 4000 ppm (0.40%) (Niles et al. 2002). The maximum tolerable dietary sulfur level for ruminants is 0.50% when the diet contains at least 40% forage (National Research Council 2005). Some specific dietary constituents known to have high sulfur content may need to be removed from the ration. These may include cruciferous forages (Brassica spp.), molasses, gypsum (calcium sulfate dihydrate), and ammonium sul­fate. The latter may be in use in some goat herds as a sup­plement to acidify urine where urolithiasis is a problem. To avoid the risk of sulfur toxicity, ammonium chloride should be used for that purpose instead of ammonium sulfate.

Enzootic Ataxia and Swayback

Nutritional copper deficiency can lead to neuronal degen­eration and secondary demyelination in the CNS and result in progressive paresis of young lambs and kids. The term swayback is applied to the congenital form of this condi­tion, while enzootic ataxia refers to the condition if it develops after birth. Both are discussed here. Some authors consider the terms synonymous.

Etiology

In sheep, nutritional copper deficiency of the ewe during the second half of pregnancy leads to abnormal maturation and subsequent degeneration of neurons and myelin in the developing fetus and the lamb postnatally. The clinical and pathologic similarities of enzootic ataxia in kids to the con­dition in lambs suggest that the cause is similar, if not iden­tical, in both species.

The problem with attributing caprine enzootic ataxia and swayback solely to copper deficiency is that in some reports of naturally occurring disease, serum, and tissue copper levels in clinically affected kids and their dams are not always low. In some instances, unaffected control ani­mals have even lower copper levels. Nevertheless, the ces­sation of additional cases through copper supplementation in affected goat herds supports copper deficiency as play­ing a central role in the development of the disease in goats. It is very likely that caprine enzootic ataxia and swayback are metabolic diseases of complex origin with conditioned copper deficiency at the core.

Epidemiology

Enzootic ataxia and swayback in goats have been reported from California, New York, Massachusetts, and Louisiana in the United States (Cordy and Knight 1978; Summers et al. 1980; Lofstedt et al. 1988; Banton et al. 1990), Saskatchewan in Canada (Brightling 1983), Argentina (Dubarry et al. 1986; Bedotti and Sanchez Rodriguez 2002), Brazil (Silva et al. 2014), Scotland (Barlow et al. 1962; Owen et al. 1965), the Netherlands (Wouda et al. 1986), Germany (Winter et al. 2002), Switzerland (von Beust et al. 1983), Kenya (Hedger et al. 1964), Ethiopia (Roeder 1980), India (Prasad et al. 1982), Australia (O'Sullivan 1977; Seaman and Hartley 1981), and New Zealand (Black 1979).

Copper deficiency in goats can either be primary, caused by low copper levels in soil and forages raised on that soil, or secondary (conditioned), when normal amounts of cop­per are present in soils and feeds, but uptake and absorp­tion are impeded by the presence of copper antagonists such as molybdenum, iron, manganese, cadmium, lead, and sulfates.

A genetic predisposition was postulated in the Netherlands, where dwarf goats were disproportionately represented in a review of 23 cases (Wouda et al. 1986). Breed and family line predispositions play a role in the dis­ease in sheep, presumably through differences in intestinal absorption and storage efficiency of copper.

Pathogenesis

Copper plays an essential role in a number of metabolic and developmental functions, serving primarily in tissue oxidation-phosphorylation reactions as part of the cytochrome oxidase system. Copper is specifically involved in myelination, osteogenesis, hematopoiesis, hair pigmen­tation, and normal growth (Brewer 1987). The role of cop­per in myelination is believed to involve phospholipid metabolism for production of normal myelin nerve sheaths.

In congenital copper deficiency or swayback, severe, pro­longed copper deficiency in the dam affects the normal development of myelin throughout the entire CNS of the developing fetus. This form occurs frequently in lambs and is associated with cavitating lesions of the cerebrum. It is rare in kids. Microcytic anemia and fragility of long bones occasionally have been observed in swayback kids, reflect­ing the roles of copper in hematopoiesis and osteogenesis, respectively. In contrast to swayback, the postnatal disease enzootic ataxia develops when copper deficiency occurs later in gestation, when the deficiency is less severe, or when the deficiency continues in offspring after birth. Neuronal death and myelin degeneration occur, but are more limited to the spinal cord, brain stem, and sometimes the cerebellum (Cordy and Knight 1978; Wouda et al. 1986).

Clinical Findings

Male and female kids of all breeds can be affected. In con­genital copper deficiency (swayback), kids are abnormal at birth. They are weak and most are unable to rise unas­sisted, but may stand unsteadily if helped to their feet. Muscle tremors and persistent nodding or shaking of the head are characteristic signs. Teeth grinding also occurs variably. Affected kids are able to suckle, vocalize, see, and hear. With intensive nursing care, these kids may live from several days to several weeks.

In the delayed form of the disease, enzootic ataxia, kids are born normally and develop a progressive paresis begin­ning as early as 1 week or as late as 28 weeks of age. The mean age of onset is 13 weeks. The clinical course varies from 1 to 14 weeks and, at least in the early stages, kids remain bright and alert and continue to eat. Early signs include weakness, fatigue, tremors, difficulty in rising, and incoordination. Symmetrical paresis and ataxia are usually observed first in the hindlimbs, but sometimes in the fore­limbs first. The signs are never unilateral. Periodic spasmodic contractions of the hindlimbs and overstretch­ing of the tarsal joints may occur. Hypermetria has been noted when there is cerebellar involvement. Laryngeal stri­dor was noted in a kid with involvement of the recurrent laryngeal nerve, a sign reported in adult goats with copper deficiency in Brazil (Sousa et al. 2017).

Affected kids may adopt a straddle-legged posture and collapse from weakness after standing a few minutes. Kids with forelimb involvement may drop onto their knees, while kids with hindlimb involvement adopt a dog-sitting position and pull themselves along with the forelimbs. Rising becomes progressively more difficult as paresis gives way to paralysis. Permanently recumbent kids show flexor contracture of the forelimbs, spastic extension of the hindlimbs, decubital ulcers, and muscle wasting. Diarrhea may occur, but affected kids frequently have concurrent coccidiosis or helminthiasis, so attribution of diarrhea to copper deficiency is problematic. Kids with enzootic ataxia are either euthanized or succumb to secondary problems such as pneumonia.

Signs of copper deficiency in adults in affected herds are not usually noted, but may include ill thrift, diarrhea, ane­mia, and depigmentation of the haircoat.

Clinical Pathology and Necropsy

Normal blood copper levels in goats are reported to be in the range of 9.4-23.6 μmol∕L (60-150 μg∕dL or 0.6-1.5 ppm; Underwood 1981). Blood or serum copper levels less than 8 μmol∕L (50 μg∕dL or 0.5 ppm) and liver copper levels less than 20 ppm dry weight are reported to be diagnostic for enzootic ataxia in kids (Seaman and Hartley 1981). However, these low levels are not consist­ently recorded in affected goats, and considerable overlap occurs in blood and tissue copper levels among affected goats, non-affected goats from the same farm, and control goats from premises with no history of the disease (Owen et al. 1965; Cordy and Knight 1978; Wouda et al. 1986; Bedotti and Sanchez Rodriguez 2002). Numerous animals in suspect herds must be tested to assess the overall cop­per status in the herd.

A microcytic anemia may be seen in affected kids, and hemoglobin values in the range of 5-7.7 g/dL have been reported (Hedger et al. 1964). Analysis of CSF has been performed infrequently and most reported cases of enzo­otic ataxia had concurrent CAE retroviral infections, so the significance of moderate pleocytosis and elevated protein in the CSF is not clear (Summers et al. 1980). In one uncomplicated case of enzootic ataxia, the CSF was normal (Lofstedt et al. 1988).

At necropsy, the cavitation and gelatinization of the cer­ebral hemispheres common in lambs with swayback have not been seen in affected kids. Neither are gross lesions evident in the CNS of kids with enzootic ataxia. These kids are usually emaciated and show evidence of muscle atrophy.

Microscopic lesions are most common in the brain stem and spinal cord. The lesions are bilaterally symmetrical. Neuronal degeneration and demyelination are characteris­tic. Swelling of the neuronal cytoplasm with shrunken nuclei and marked chromatolysis is typical. Wallerian degeneration and loss of myelinated axons with gliosis and phagocytosis are evident. Cerebellar atrophy or hypoplasia may also be noted, with degeneration of Purkinje cells and reduced thickness of molecular and granular cell layers (Cordy and Knight 1978; Wouda et al. 1986).

Diagnosis

Definitive diagnosis is based on determination of low tis­sue copper levels and characteristic lesions at necropsy. A presumptive diagnosis ante mortem is based on the typical clinical presentation, evidence of low copper levels or the presence of copper antagonists in the diet, low tissue cop­per levels, and a therapeutic response to treatment with copper compounds in mildly affected kids.

For congenital copper deficiency, the differential diagno­sis includes hydrocephalus, congenital vertebrospinal abnormalities, caprine beta mannosidosis, border disease, hypoglycemia, and hypothermia. There is also a reported case of granulomatous encephalitis in a newborn kid due to congenital infection with Neospora caninum, which pro­duced signs similar to those of congenital copper defi­ciency (Corbellini et al. 2001). This protozoal parasite is more commonly associated with abortion and is discussed further in Chapter 13.

For delayed copper deficiency, the neurologic form of CAE, vertebral trauma, spinal abscesses, cerebrospinal nematodiasis, nutritional muscular dystrophy, floppy kid disease (as described in Chapter 19), and listeriosis must be ruled out. In the early stages of disease, ascending paralysis caused by rabies is also a diagnostic consideration. Numerous cases of enzootic ataxia concurrent with CAE have been reported, which complicates the diagnosis (Summers et al. 1980; Lofstedt et al. 1988).

Treatment

Mildly affected congenital cases, and early cases of enzo - otic ataxia, may respond favorably to treatment with cop - per compounds, but complete recovery is uncommon. If desired, blood and liver biopsy specimens should be taken before treatment so that interpretation of tissue copper levels is not confused. Copper glycinate has been reported as an effective treatment given parenterally to kids as a single total dose of 60 mg (Seaman and Hartley 1981).

Control

Effective control depends on determining the underlying cause of copper deficiency. It may be necessary to assay feeds, water, and soils to ascertain if there is a primary copper deficiency or a secondary deficiency conditioned by excess molybdenum, sulfates, or other copper antagonists. Copper requirements are not well defined for goats. This is unfortunate, because goats appear to metabolize and store copper differently from sheep and extrapolations are proba­bly inaccurate. Nevertheless, for sheep, copper levels in vari­ous feeds should be at least 5ppm and molybdenum levels should not exceed 5ppm. The copper-to-molybdenum ratio in the overall diet should be kept between 5 : 1 and 10 : 1 (Rankins et al. 2002). The current dietary copper recommen­dation for goats, as discussed in Chapter 19, is 10-20ppm. Sulfate levels may be high in water and on pastures and may induce conditioned copper deficiency even when Cu : Mo ratios are within acceptable limits. Sulfate levels in feed should not exceed 3500 ppm (Black 1979). When soils are copper deficient, annual top-dressing of pasture with copper sulfate at a rate of 2-3 kg/ha is recommended.

Enzootic ataxia may be prevented by supplementation of copper. In the face of outbreaks of swayback or enzootic ataxia, pregnant does can be given copper glycinate SC at a total dose of 150 mg at mid-gestation to prevent subsequent copper deficiency in kids. Kids can be given 60 mg of cop­per glycinate SC at birth if does were not treated earlier in pregnancy. This should protect them at least through weaning. Oral copper sulfate in the drinking water of does at a dose of 1.5 g per head per week during pregnancy has also been used successfully, but may cause corrosion prob­lems in metal pipes and troughs.

The most convenient method of control is to ensure that goats always have adequate copper in the diet. Trace min­eralized salts containing copper sulfate in the range of 0.5-2% can be made available in blocks free choice or incorporated into the concentrate ration. A number of sustained-release copper products for oral administration, such as copper oxide needles in gelatin capsules, also known as copper oxide wire particles, have been used suc­cessfully in sheep in copper-deficient areas, and there is at least one report of their safe use in goats in a herd with a history of swayback, though at 15 weeks following admin­istration of 4 g copper oxide needles, copper levels in vis­cera were no different between treated and untreated goats, suggesting that the intervention may be less effective in goats than in sheep (Inglis et al. 1986). However, a report from Germany involving a goat herd with a history of pri­mary copper deficiency with associated kid mortalities indicated that administration of a commercial copper oxide wire particle bolus to pregnant does during the last trimester of pregnancy was effective in maintaining serum copper levels and mitigating further cases of enzootic ataxia (Winter et al. 2004).

Hypovitaminosis A

In cattle, vitamin A deficiency is associated with a number of clinical manifestations including lacrimation, nasal dis­charge, coughing, corneal opacity, abortion, and weak calves. Signs of neurologic dysfunction include night blind­ness, total blindness, incoordination, and convulsions. The incoordination and convulsions are due to increased intracranial pressure resulting from reduced absorption of CSF, caused by biochemical and structural alterations of the arachnoid villi associated with vitamin A deficiency.

It has been demonstrated experimentally in adult goats fed vitamin A-deficient diets that decreased absorption of CSF can result, but CSF pressure does not rise significantly and no papilledema of the optic nerve develops (Frier et al. 1974). Convulsions were not observed in either this study or an earlier one involving both adult and young, growing goats (Schmidt 1941). Signs were limited to a loss of appetite and weight, ropy nasal discharge, corneal opac­ity, and night blindness. Hypovitaminosis A is not a likely cause of convulsions in goats.