History

A 1-day-old 35-kg male mixed-breed calf was submitted for necropsy. At birth, a defect in the center of the forehead was noted. In addition, the calf was ataxic and its mucous membranes were yellow. The farm of origin of the calf had 2 abortions among mixed-breed beef cows in the preceding few months. The calf was euthanized by IV injection of an unspecified barbiturate solution.

Gross Findings

The carcass of the calf had adequate subcutaneous and visceral fat stores. Soft, multinodular connective tissue protruded through a 2 X 2-cm full-thickness defect in the bone and skin in the center of the dorsal aspect of the calvarium (Figure 1). The cranial vault was small, and the diencephalon, cerebral hemispheres, and rostral portion of the midbrain were absent. The caudal region of the brainstem, cerebellum, and spinal cord were present but dorsolaterally flattened and elongated. The cerebellum was small, oval, and flattened. The liver was diffusely golden yellow and firm. The pericardial sac contained 10 mL of yellow watery fluid. The lungs were diffusely mildly congested and floated when submerged in formalin. Dark-red cysts were present on the right and left atrioventricular valves.

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Photographs of the dorsal aspect of the head of a 1-day-old calf (A) and cross-section view of the skull and brain (B). Prior to euthanasia, the calf had been ataxic and its mucous membranes were yellow. Notice the defect in the skin and skull of the calf. On gross examination of the head in cross section, brain tissue is visible but the cerebrum is absent.

Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.857

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Histopathologic Findings

On histologic examination, marked dysplasia within the cerebellum was characterized by the presence of folia in the medullary tissue. Cerebellar white matter had vacuolation, intramyelinic edema, infiltration of a few macrophages into the parenchyma (gliosis), and multifocal hemorrhages. The remainder of the cerebellar structure appeared normal. A focal region of tall columnar epithelial cells with slightly vacuolated cytoplasm and associated mucus (identified in sections by periodic acid–Schiff reaction with Alcian blue staining and mucicarmine staining), which was presumptively identified as sinus epithelial tissue, was evident within the neuropil (Figure 2). The ventricles were distorted and flattened. Moderate neutrophilic cuffing surrounded the blood vessels, and large numbers of neutrophils were present within the vessel walls and the ventricle. Lungs contained occasional foci of yellow, homogeneous material (meconium) within alveoli. There was diffuse glycogen accumulation within the hepatocytes’ cytoplasm and multifocal cytoplasmic fatty vacuoles. One adrenal gland was dysplastic with displaced medullary cells scattered within the cortex; the contralateral adrenal gland was not examined.

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Photomicrographs of sections of the remnant neuropil adherent to the internal aspect of the defect in the skull from the calf in Figure 1. A—In this view, there is a focus of tall columnar epithelial cells, consistent with sinus epithelial tissue, and associated mucus within cerebral remnant. H&E stain; bar = 80 μm. Inset—Periodic acid–Schiff reaction with Alcian blue staining highlights mucus in the remnant neuropil (blue staining). Periodic acid–Schiff reaction with Alcian blue stain; bar = 40 μm. B—In another view, there is marked neutrophilic perivascular cuffing within the cerebral remnant. H&E stain; bar = 80 μm.

Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.857

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Laboratory Findings

Nutrient analysis of liver tissue samples revealed low vitamin A concentration (5.76 μg/g dry matter basis; in our laboratory, the reference ranges for newborns [1 to 9 days of age] and fetuses are 50.00 to 100.00 μg/g dry tissue and 8 to 40 μg/g dry tissue, respectively). Separate virus neutralization tests were applied to fetal serum for bovine viral diarrhea virus type 1 (BVDV-1) and bovine herpesvirus 1; results for both were < 1:4. There were no other notable laboratory findings.

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: prosencephalic hypoplasia with cranioschisis and encephalocele and vitamin A deficiency in a calf.

Comments

For the calf of the present report, the most important lesions were cerebral aplasia (prosencephalic hypoplasia) with cranioschisis and encephalocele. The inflammatory changes were likely attributable to cranioschisis and exposure of the brain to the external environment. Ancillary laboratory testing revealed that there was a concurrent vitamin A deficiency in this 1-day-old calf.

The causes of cerebral aplasia in cattle are not well understood. Teratogenic effects of vitamin A excess and vitamin A deficiency have been identified in experimental studies in humans and other animals.^1–3 In the case described in the present report, it was likely that the vitamin A deficiency had a role in the development of the brain abnormality. Clinically, hypovitaminosis A in adult cattle is most often associated with blindness and ocular abnormalities; however, nutrient deficiencies can also have a major impact on reproduction. Congenital deformities, abortion, birth of weak calves, retained fetal membranes, and metritis have been observed in cattle with vitamin A deficiency.^4,5 Vitamin A deficiencies can have an impact on reproduction even when clinical signs of hypovitaminosis are not evident.⁴ Vitamin A is involved in the development of many body systems, including the skeletal and nervous systems.⁶ In pregnant animals, the duration of vitamin A deficiency directly impacts the type and severity of lesions observed in the offspring. In instances of abortion and congenital abnormalities in cattle, nutrient analysis and evaluation of the diet is often warranted.

Vitamin A deficiencies can occur in beef cattle grazing on pasture during droughts.⁴ Forage is also typically very low in vitamin A content and, after it is harvested, the vitamin A concentration within the forage decreases as a result of oxidation.⁷ In the spring of 2013, examination of submission data to the Iowa State University Veterinary Diagnostic Laboratory revealed that liver samples from almost all weak and stillborn calves had vitamin A concentrations < 1 ppm (although whether that finding was determined on a dry or wet matter basis was not reported); the concentration range expected for healthy calves was 12 to 32 ppm.⁷ In a separate study,⁸ calves with serum vitamin A concentrations in the lowest quartile were 2.8 times as likely to die as calves with higher serum vitamin A concentrations. In the case described in the present report, the reference ranges for liver tissue vitamin A concentration used were based on established in-laboratory ranges (5th to 95th percentile of cases) for both neonates (1 to 9 days of age) that likely had nursed and fetuses that had not nursed because consumption of colostrum can markedly affect vitamin A concentration.⁷ The liver tissue vitamin A concentration for the calf of the present report was less than the lower limit of either reference range. To prevent complications associated with hypovitaminosis A among bovine fetuses and neonates, recommendations to producers include administration of supplemental vitamin A during the last third of pregnancy to cows that are receiving low-quality forage. Weak calves that are vitamin A deficient should receive an IM injection of 500,000 U of supplemental vitamin A.^7,9