JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 1757043): Angora goat kid
HISTORY: This kid was found in sternal recumbency. During the subsequent two weeks, it was unable to walk or rise but remained alert and continued to eat and drink. Limb withdrawal reflexes were normal.
HISTOPATHOLOGIC DESCRIPTION: Spinal cord: Primarily affecting the medial aspect of the ventral funiculus, and to a lesser extent, the dorsal aspect of the lateral funiculus there is bilaterally symmetrical, focally extensive vacuolation (spongiosis) of the white matter. Myelin sheaths are dilated up to 70 um in diameter and occasionally contain swollen axons (spheroids), eosinophilic debris, or rarely foamy gitter cells (ellipsoids) (Wallerian degeneration). Scattered motor neurons in the ventral horn of the gray matter are swollen up to 70 um in diameter, and contain pale eosinophilic, homogenous central cytoplasm with peripheral dispersion of Nissl substance and eccentrically placed nuclei (central chromatolysis). Occasionally ventral spinal nerves contain similar changes with swollen myelin sheaths containing spheroids or gitter cells.
MORPHOLOGIC DIAGNOSIS: Spinal cord, white matter, ventral and lateral funiculi; ventral spinal nerve roots: Neuroaxonal degeneration, bilaterally symmetrical, multifocal, moderate, with ventral horn neuronal chromatolysis, Angora, caprine.
ETIOLOGIC DIAGNOSIS: Nutritional neuroaxonal degeneration
CAUSE: Copper deficiency
CONDITION: Enzootic ataxia
CONDITION SYNONYMS: Swayback
· CNS disease of lambs and goat kids due to copper deficiency
· Two syndromes:
o Congenital (swayback; primarily lambs, rarely kids)
o Delayed onset, up to 6 months (enzootic ataxia; both lambs and kids)
· Copper deficiency may be primary or secondary:
· Primary: Dietary deficiency; copper deficient soil or forage
o Secondary: More common; reduced absorption from gut, reduced availability in tissues or enhanced excretion
o Unique in ruminants: Molybdenum and sulfate limit copper absorption by forming complexes with copper called thiomolybdates
· Experimental iron exposure has been demonstrated to induce hypocupremia
· Copper is required for:
o Superoxide dismutase – antioxidant activity
o Cytochrome c oxidase – mitochondrial respiration
o Dopamine beta-hydroxylase – catecholamine synthesis
o Tyrosinase – melanin synthesis
o Protein ceruloplasmin – iron homeostasis
· Hypocuprosis also affects the integument (achromotrichia, straight wool/”steely wool”, impaired keratinization), musculoskeletal development (osteoporosis), connective tissue integrity, and causes anemia
· Pathogenesis is poorly understood
· Altered function of mitochondrial enzyme cytochrome oxidase may lead to energy failure and subsequent neuronal degeneration
· Cerebral lesions may result from loss of embryonic cells during brain development or to dysgenesis due to biochemical disturbance
· A mutation in the enzyme copper-zinc superoxide dismutase, observed in humans with familial amyotrophic lateral sclerosis may play a role
TYPICAL CLINICAL FINDINGS:
· Congenital (swayback): Most common in lambs; unable to rise, blind, deaf, swaying, falling, spastic paralysis, and death within first few days of life, occasionally stillborn
· Delayed onset (enzootic ataxia): More common in goat kids; normal at birth; progressive development of motor disturbances including swaying, ataxia, gait deficits, limb paresis, and death within 6 months
TYPICAL GROSS FINDINGS:
· Congenital (swayback): 50% of animals have bilaterally symmetrical cerebral cortical softening or cavitation
· Delayed (enzootic ataxia): Few or no gross lesions
· Rarely, cerebellar degeneration in lambs and goat kids; acute cerebral edema in lambs
TYPICAL LIGHT MICROSCOPIC FINDINGS:
· Brainstem and spinal cord lesions are similar in lambs & kids in both congential & delayed-onset forms
· Spinal cord
o Gray matter: Loss of Nissl substance (central chromatolysis), eccentric and pyknotic nucleus, eosinophilic cytoplasm, necrosis
o White matter: Bilateral areas of pallor from degeneration of myelinated axons in the dorso-lateral aspect of the lateral funiculi (corresponding to the spinocerebellar tracts) and ventro-medial aspect of the ventral funiculi adjacent to the ventral median fissure
· Brain stem: Similar lesions to spinal cord, with scattered distribution
· Cerebellum: Lesions only present in kids and consist of Purkinje and granular layer thinning, degeneration and necrosis; and hypertrophy of the molecular layer (Bergmann’s glial cell processes)
· Chromatolytic neurons have depletion of ribosomes and aggregates of enlarged, mitochondria, and abundant fascicles of neurofilaments
· Primary axonal degeneration with secondary loss of myelin
ADDITIONAL DIAGNOSTIC TESTS:
· Plasma, serum or tissue (liver, CNS) concentration of copper; concentrations below 25-150 ppm in goat livers (wet weight) is considered deficient
· Microcytic hypochromic anemia that is unmanageable with iron
· Luxol fast blue, Cresyl violet
· Bluetongue (Reoviridae, Orbivirus): Infection of dam results in cerebral anomalies in lambs including porencephaly
· Border disease (Flaviviridae, Pestivirus): Infection of dam causes CNS abnormalities of lambs or goats, including hypomyelination, porencephaly-hydranencephaly, cerebellar hypoplasia, microencephaly and decreased diameter of the spinal cord
· Cache Valley Fever (Bunyaviridae, Bunyavirus): Infection results in hydranencephaly, microencephaly, cerebellar hypoplasia, and absence of the ventral horn neurons in the spinal cord of lambs
· Akabane (Bunyaviridae, Bunyavirus): Infection results in porencephaly, hydranencephaly, and ventral horn degeneration in spinal cord of various ruminant species in Japan, Australia, Israel
· Rift Valley Fever (Bunyaviridae, Phlebovirus), hydranencephaly in lambs in Africa
· Piglet: Wallerian degeneration in the brain stem and spinal cord white matter, no neuronal changes; skeletal abnormalities leading to fractures; elastin formation abnormalities in the aorta and pulmonary arteries leading to rupture
· Young adult deer: Syndrome and lesions similar to enzootic ataxia with progressively stiff gait, swaying, and recumbency that leads to death; spinal cord demyelination and midbrain neuronal degeneration; osteochondrosis, poor hair coat
· Male brindled mottled mouse mutant: Animal model of Menke’s disease (kinky hair syndrome)
· Humans (Menkes’ disease): An X-linked disorder of defective ATPase7A with impaired transfer of copper out of enterocytes, resulting in hypocuprosis; many features similar to copper deficiency in animals; syndromes include muscle weakness, neurologic defects, hypopigmentation, abnormal collagen cross-linking
· Cattle: Primary copper deficiency results in unthriftiness, poor hair coat (achromotrichia), loss of milk production, and anemia in adult cattle; poor growth and long bone fractures in calves; secondary copper deficiency is similar with anemia occurring less frequently and diarrhea (“peat scours”) occurring more frequently
· Sheep: “Steely wool”, osteoporosis, hypopigmentation of black wool
· Long-Evans cinnamon rat and toxic milk mutant mouse – animal models of Wilson’s disease (hepatolenticular degeneration), an autosomal recessive disorder of defective ATPase7B disrupts ceruloplasmin formation resulting in excess hepatic, cerebral, renal and corneal copper accumulation
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