CASE NOTES

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A severe outbreak of both congenital and acquired copper deficiency in Spanish lambs

Maialen Zinkunegi¹, Isabel Cuartielles², Raquel García¹, Arthur Cobayashi¹, Pilar Trejo¹, Miriam Lazpita¹, Paula Jiménez¹, Janire Fernandez¹, Lucía Rodriguez¹, Álex Gómez¹, María Climent^1,3, Delia Lacasta¹
1 Ruminant Clinical Service of the Veterinary Faculty of Zaragoza (SCRUM). Animal Pathology Department, C/ Miguel Servet 177. 50013, Zaragoza, Spain
2 Grupo Pastores. Zaragoza. Spain
3 Anatomy and embryology Department, University of Zaragoza, / Miguel Servet 177. 50013, Zaragoza, Spain

Posted Flock & Herd August 2024

Introduction

Enzootic ataxia is a congenital or acquired disease caused by copper deficiency. The congenital form (swayback) is characterised by lambs that are stillborn or born weak, unable to stand and with tetraparesis. These usually die within the first week of life. The acquired or late form is characterised by incoordination, weakness and hindlimb paresis. This form frequently presents in lambs older than three weeks. The congenital presentation is associated with the mother's copper deficiency during the last third of pregnancy when foetal mineralisation occurs. The acquired form is associated with copper deficiency in suckling and young fattening lambs. Both copper deficiencies can also be caused by an excess of copper antagonists in the diet.

History

A Spanish semi-intensive farm of 500 INRA 401 sheep and males of Salz X Dorper Ethiopian black spot genetic lines presented with a neurologic syndrome in 80% of the neonates during the last lambing period. The production system was based on three lambing periods per year, with twin parturitions in most cases. During gestation, the animals were kept indoors and fed a diet based on last-cut alfalfa silage, with 24% protein, TEFF silage and vetch silage. They also had access to mineral blocks and salt as a supplement. Every animal was correctly dewormed after coprological tests and vaccinated against enterotoxaemia.

Affected newborn lambs presented with severe ataxia, causing inanition and death. Additionally, 2-3% of the fattening lambs of the previous lambing period developed hindlimb paresis after weaning. Four affected lambs, three nursing lambs (three days old) and one fattening lamb (four months old), were referred to the Ruminants' Clinical Service (SCRUM) of the University of Zaragoza, Spain.

One of the nursing lambs arrived dead (lamb nº1), and it was referred directly to the Pathological Service of the Faculty for pathological study. The three remaining lambs were clinically examined, and some complementary tests were performed. Finally, one nursing lamb (lamb nº2) and the fattening lamb (lamb nº4) were humanely euthanised, and pathological studies were performed. The last nursing lamb (lamb nº3) was used for treatment evaluation.

Clinical findings

A complete clinical examination and haematology were performed. In addition, a more detailed neurological examination was conducted. All animals presented with a lack of a menace response and hindlimb ataxia. Additionally, nursing lambs showed tremors, hyperextension (lamb nº2) and pedalling (lamb nº3), all related to intracranial lesions. In contrast, the fattening lamb showed hindlimb paresis with retention of the spinal reflexes, which was consistent with an injury at the lower motor neuron level.

COMPLEMENTARY TESTS

The haematology of the three animals revealed microcytic anaemia. In the fattening lamb, microcytic anaemia could have been associated with an iron deficiency, which could have been related to a copper deficiency, as copper participates in iron metabolism. Likewise, the nursing lambs showed leukopenia with lymphopenia and eosinopenia, which could have been due to an immunodeficiency. Biochemical analysis also revealed reduced renal and hepatic function in all three animals.

With the aim of delving deeper into the diagnosis of the neurological disorder, a computed tomography (CT) scan was performed on one of the nursing lambs. Small, diffuse and radiolucent lesions throughout the entire cerebral and cerebellar cortex were observed, which were interpreted as multifocal necrotic hypodense lesions at the level of the right thalamus and cortex (Fig. 1). Additionally, a deviation of the longitudinal fissure of the brain to the right was observed (Fig. 2). These findings revealed a generalised lack of white matter and a lack of vascularisation in the cerebral cortex. In addition, through the presence of a radiolucent sulcus in a frontal section, we could observe cortical atrophy with some spaces filled with fluid, indicating that the brain size was reduced (Fig. 1). Deeper within the brain, it appeared vacuolated, indicating brain tissue atrophy.

Figure 1. Frontal section of the CT scan where small, diffuse and radiolucent lesions throughout the entire cerebral and cerebellar cortex were observed. Radiolucent sulcus (cortical atrophy) with some spaces filled with fluid (reduced brain size) were also visible.

>Figure 2. Frontal section of the CT scan. Deviation of the longitudinal fissure of the brain to the right was observed.

PATHOLOGICAL FINDINGS

At necropsy, bilateral symmetrical cystic cavitations involving the white matter of cerebral hemispheres (porencephaly) were observed in lambs nº1 and nº2 (Fig. 3). Additionally, severe white matter atrophy was detected in the brain of the lamb nº2 (Fig. 4) and in the lumbar spinal cord of the fattening lamb (lamb nº4).

Figure 3. Nursing lamb nº1. Cerebrum: bilateral symmetrical cavitations (arrows) of white matter (porencephaly).

Figure 4. Nursing lamb nº2. Cerebrum: severe white matter atrophy (arrows).

Histopathological study of the cerebrum confirmed marked white matter atrophy/degeneration (Fig. 5a). Diffusely, a high number of glial cells, principally composed of astrocytes and gitter cells (gliosis), was observed. The spinal cord presented a marked degeneration of myelinated axons (Wallerian-like degeneration) and loss of Nissl substance of motor neurons (central chromatolysis) with eccentric and pyknotic nuclei (Fig. 5b).

Figure 5. Nursing lamb nº2. (a) Cerebrum: marked diffuse white matter degeneration (arrow). H-E. (b) Spinal cord: multifocal degeneration of myelinated axons (arrows). H-E.

Discussion

Clinical signs suggested a differential diagnosis list that included Schmallenberg disease (Endalew et al., 2019), Border disease (Barlow, 1980; García-Pérez et al. 2009), toxic plant poisoning (Panter et al., 2013; Soler & de Jesús Roy, 2003), and congenital copper deficiency (Rizwan et al. 2016). Neurological examination, CT scan and pathological findings confirmed a diagnosis of copper deficiency (Balbuena et al., 2003; Ozkul et al. 2012). The viral molecular analyses of the nervous tissue were all negative.

Copper deficiency has two presentations. Swayback occurs in neonates due to a mother's copper deficiency during pregnancy. This condition is characterised by lambs born either dead or unable to stand, tetraparesis, and death within the first week of life. On the other hand, enzootic ataxia (EA) is due to copper deficiency after lambing. These animals are born healthy with clinical signs such as incoordination, weakness, paresis of the hindquarters and paraparesis appearing after the third week of life (Radostits et al. 2002). In our case, both presentations appeared simultaneously in lambs from two consecutive lambing periods. This finding was probably due to an initial deficiency of copper in the milk of the mothers of the affected lambs, causing the late form, which subsequently became much more severe, affecting the development of the nervous system during the following pregnancy.

The origin of copper deficiency may be primary, due to insufficient levels of copper in the mother's diet, or secondary, due to the presence of antagonists, such as molybdenum, gypsum (hydrated lime sulphate), iron and zinc. These antagonists decrease the availability of copper due to the formation of insoluble salts (Kutlu et al., 2018), as occurred in the presented case.

Swayback is characterised by defective myelination of the neonate's nervous system. Therefore, the development of EA is linked to the timing of the copper deficiency in relation to myelination in the foetus. This process begins in the brain, then the spinal cord, and finally, the peripheral nerves. In the brain, a few weeks before lambing, myelination ends. Myelin deposition in the spinal cord and peripheral nerves concludes by the end of the first month postpartum (Carosio et al. 2022).

Preventing congenital copper deficiency involves feeding adequate levels of copper to the ewe during gestation. Normally, a balanced ration is sufficient. However, in cases of chronic deficiencies, 0.2% copper sulphate can be added to the mineral mixture. Slow-release intraruminal boluses are another option.

Other elements that act as antagonists of copper, such as molybdenum or iron, should be considered when adjusting the daily diet of animals on the farm to ensure that copper can properly perform its functions in the body. It is crucial to pay special attention during spring and autumn, periods in which the concentration of these elements increases in plants (Helmer et al. 2021).

When pathology due to deficiency is widespread on the farm, and after an economic assessment of the costs, affected animals may receive copper supplements orally or parenterally as a treatment. Many of the changes in the central nervous system seem to be irreversible, and copper supplementation may have little effect, emphasising the value of prevention. However, lamb nº3, fed artificially with calf milk with a copper concentration of 0.5 mg/kg (higher than lamb milk), showed significant improvement with the resolution of clinical signs. The CT scans continued to show brain lesions.

Copper deficiency is preventable by paying adequate attention to both copper and its antagonists, especially during the last weeks of gestation, a crucial time in myelination of the foetus. It is also essential to adhere to the recommendations for copper intake to avoid overdosing leading to liver accumulation and copper toxicity.

References

1. Balbuena O, McDowell L, Mahyew I et al. (2003) Ataxia enzootica tardía en corderos. Contribución al conocimiento de su etiología en el Chaco (Argentina)
2. Barlow RM (1980) Morphogenesis of hydranencephaly and other intracranial malformations in progeny of pregnant ewes infected with pestiviruses Journal of Comparative Pathology 90:87-98 doi.org
3. Carosio A, Bengolea A, Sager R et al. (2022) Ataxia enzoótica tardía en corderos asociada a deficiencia de cobre en una majada de la región semiárida central Argentina. Zenodo (CERN European Organization for Nuclear Research) zenodo.org
4. Endalew AD, Faburay B, Wilson WC et al. (2019) Schmallenberg Disease—A newly emerged Culicoides-Borne viral disease of ruminants Viruses 11:1065 doi.org
5. Fuentes Pérez O (1992) Enfermedades neonatales de los corderos MG Mundo ganadero 63-70 dialnet.unirioja.es
6. García-Pérez AL, Minguijón E, Estévez L et al. (2009) Clinical and laboratorial findings in pregnant ewes and their progeny infected with Border disease virus (BDV-4 genotype) Research in Veterinary Science/Research in Veterinary Science 86:345-352 doi.org
7. Helmer C, Hannemann R, Humann-Ziehank E et al. (2021) A Case of Concurrent Molybdenosis, Secondary Copper, Cobalt and Selenium Deficiency in a Small Sheep Herd in Northern Germany Animals 11:1864
8. Kutulu T, Yurdagul Ozsoy S, Ozyìldìz Z (2018) Histopathologic examination of the brain tissue in lambs with neurological symptoms: Enzootic ataxia Veterinary Journal of Mehmet Akif Ersoy University 3:64-70
9. Ozkul IA, Alcigir G, Sepici-Dincel A et al. (2012) Histopathological and biochemical findings of congenital copper deficiency: are these similar to those of caprine arthritis-encephalitis? Journal of Veterinary Science 13:107 doi.org
10. Panter KE, Welch KD, Gardner DR et al. (2013) Poisonous plants: Effects on embryo and fetal development Birth Defects Research 99:223-234 doi.org
11. Radostits OM & Done SH (2008) Veterinary medicine: a textbook of the diseases of cattle, horses, sheep, pigs and goats 10th ed., reprint. Saunders Elsevier
12. Soler Rodríguez F & De Jesús Roy Pérez T (2003) Plantas que afectan a la reproducción Ovis 57-65 dialnet.unirioja.es
13. Van Saun RJ (2023) Trace mineral nutrition of sheep Veterinary Clinics of North America: Food Animal Practice 39:517-533 doi.org