FINAL DIAGNOSIS - Skull malformation Vitamin A deficiency

Signalment: A 1-1/2 year old, 280 pound. captive, intact male African lion

Clinical history:

The lion was presented with a history of progressive ataxia and generalized weakness.  Bloodwork showed elevated amylase, CPK, canine distemper antibody titers of 1:8 and negative antigen.  Initial response to dexamethasone was short-lived.  Tensilon test was negative.  A muscle biopsy was normal.  The lion continued to eat well, with a normal mental status, but remained ataxic.  Two months after initial presentation, the lion had an acute onset of recumbency and tonic-clonic rigidity.  The owners requested euthanasia.

Necropsy Findings:

  The atlanto-occipital joint was immobile due to complete fusion of the atlas to the occipital bone, and had a slight deviation to the left of the spinal axis.  The dens of the axis was curved dorsally and to the left, causing pressure on the ventral portions of the cervical spinal cord, which was slightly flattened.  The caudal portions of the calvarium were markedly thick, the occipital bone being 3 cm thick and the parietal bone being 2 cm thick.  The osseous tentorium cerebelli, normally a thin ossified membrane, was 1 cm thick and 1.5 cm long, forming a hard knob compressing the cerebellum and portions of the cerebrum.  The vermis of the cerebellum was coned and protruded into the foramen magnum.  Small amounts of blood surrounded the brain stem at the level of the cerebellar herniation.

Histopathology:

  Lesions were primarily observed in sections of cranial bones and spinal cord.  The bone changes were characterized by marked proliferation of bone, which consisted of increased numbers of loosely spaced, irregular spicules of lamellar and, to a lesser extent,  woven bone, and little evidence of bone resorption.  Spinal cord changes consisted of Wallerian-type degeneration, which was most prominent in the white matter of the ventral funiculi.  The axon sheaths were ballooned and either contained swollen, pale eosinophilic axons, or a few macrophages and no axons.  There was multifocal dissecting interstitial astrocytosis in degenerate areas.

Morphologic diagnoses:

1) Atlanto-occipital malformation with ankylosis

2) Hypertrophic osteopathy in occipital bone, parietal bone, and osseous tentorium cerebelli

3) Degenerative myelopathy due to compression

Ancillary tests:

 Selenium (0.38 ppm) and vitamin E (20.48 ppm) levels in the liver, and 25-OH-vitamin D3 (nMol/L) levels in the kidney were within the normal reference range for dogs.  However, the vitamin A levels in the liver were undetectable (0.0 micrograms/g).

Discussion:

  Similar cranial bone lesions have been described in captive African lions in Europe, South Africa, Australia, Israel and Florida.  It has been attributed in most cases to vitamin A deficiency, although a genetic or familial basis has also been suggested.  Vitamin A sustains development and differentiation of epithelial structures and bone.  Vitamin A stimulates osteoclast activity, causing them to increase acid phosphatase content and resorb bone and, for this reason, excesses and deficiencies of this vitamin have an impact in bone development.  Vitamin A excess is characterized by injury to growth cartilage, osteoporosis, and developmental exostosis.  In kittens, for example, the occipital bone may be so thin that the cerebellum can be crushed by manual pressure to the overlying skin, and osteophyte formation may lead to a deforming cervical spondylosis.  On the other hand, vitamin A deficiency in pigs, cattle, and dogs has been associated with thickening of cranial bones, especially the tentorium cerebelli.  The pathogenesis of these skeletal changes is related to altered patterns of drift in bones that are growing during the period of deficiency.  Normally, osteoclasts are responsive to vitamin A and, in the cranium of deficient animals, there is inadequate resorption of endosteal bone.  Bone is often produced in sites where resorption should be occurring.

  The liver vitamin A levels in this case were undetectable and, in other reports, they ranged from undetectable to 48 micrograms/g of tissue, compared to a value of 1,636 micrograms/g reported as a control in a normal, 2-year-old wild lion.  According to the National Research Council of the USA, liver vitamin A levels in fully grown animals should be 300 micrograms/g or greater, and a value of less than 40 micrograms/g should be considered a dietary deficiency.  Felids have a high vitamin A requirement compared to other species, and deficiencies are frequently encountered in captive cats.  Frequent vitamin A supplementation, or addition of bovine liver (which contains large amounts of vitamin A) to the diet, may be necessary to prevent these abnormalities in lions.  However, the nutritional requirements for many zoo animals have not been completely determined and care must be taken to prevent vitamin deficiencies or excesses.

 - by Marlon Rebelatto, DVM

    ADDL Graduate Student