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HYPOVITAMINOSIS A has been reported to alter osteoblastic and osteoclastic activity in young animals, resulting in defective remodelling of cranial membranous bones, particularly the occipital and sphenoid bones, with subsequent caudal fossa overcrowding and herniation of the cerebellar vermis into the foramen magnum (Thompson 2007) and with associated neurological dysfunction.
A six-month-old female captive-bred cheetah (Acinonyx jubatus) was presented to the Neurology-Neurosurgery Service at the Animal Health Trust with a three-week history of progressive ataxia, impaired balance and nystagmus. Treatment with amoxicillin and steroids (dexamethasone injection and oral prednisolone) for six days had not resulted in any improvement. Haematology, serum biochemistry and chest radiographs taken before referral were normal. The cheetah was the only surviving cub of a litter of five that had resulted from the accidental mating of a mother and son. The cause of death of the four littermates was unknown. The cheetah had been hand-reared on kitten milk replacer (KMR ; Pet Ag) and since being weaned at three months of age had been fed raw lean red meat (horse and beef) with calcium supplementation (Carnivore calcium; Zoovet Products, International Zoo Veterinary Group). It had been vaccinated against feline parvovirus, feline herpesvirus type 1 (FHV-1), feline calicivirus and Chlamydophila felis with a multivalent vaccine (Fevaxyn i-CHPchlam; Fort Dodge Animal Health). General physical and neurological examinations could be performed almost as commonly done in domestic cats, as the cheetah was used to close interaction with human beings. The only abnormalities on general physical examination were increased salivation and neurological deficits. The neurological examination revealed slightly depressed mental status and cerebellovestibular ataxia. Proprioception was difficult to assess but appeared to be decreased. The withdrawal reflex was normal in all four limbs. Cranial nerve examination revealed an absent menace response bilaterally and constant horizontal pendular nystagmus, which became rotatory or vertical when the animal was in dorsal recumbency. The clinical neuroanatomical localisation was to the cerebellum/central vestibular system. However, a multifocal intracranial neuroanatomical localisation could not be excluded. The differential diagnosis included infectious/inflammatory aetiologies, congenital anomalies, metabolic and nutritional disorders.
Haematology, urinalysis and abdominal ultrasonography were normal. A comprehensive serum biochemistry panel revealed mild hypoproteinaemia (49 g/l, reference range 57 to 80 g/l) and hypoglobulinaemia (20 g/l, reference range 24 to 47 g/l). An ophthalmic examination, including fundus examination, performed during general anaesthesia, was unremarkable. MRI of the brain showed overcrowding of the caudal fossa, compression of the caudal cerebellar vermis and herniation through the foramen magnum, dorsal flattening of the medulla oblongata, and effacement of the fourth ventricle (Fig 1). In addition, the exoccipital, basioccipital and basisphenoid bones and the tentorium cerebelli osseum were subjectively thickened. Lumbar cerebrospinal fluid (CSF) analysis revealed zero white blood cells/μl and a total protein concentration of 0.20 g/l, both of which are within the normal ranges for domestic felids. PCR tests on CSF for canine distemper virus, Toxoplasma gondii, Neospora caninum, FHV-1, Borna disease virus, feline leukaemia virus, feline immunodeficiency virus and feline coronavirus were negative. The blood vitamin B1 level was within the reference range for domestic felids. The serum vitamin A concentration was <0.1 μmol/l (reference range for cheetahs 1.7 to 4.6 μmol/l) (Bechert and others 2002).
The cheetah was discharged on 15 mg/kg clindamycin (Antirobe; Pfizer), administered orally twice a day, and 200 mg vitamin B1 (Thiamin; Holland & Barrett), administered orally once a day, pending the results of the PCRs on CSF and the blood vitamin A and B1 blood levels. The animal continued to deteriorate during the following week, and these treatments were discontinued. Oral supplementation with 15,000 iu/day vitamin A was started by administration of a multivitamin and mineral complex (Aquavits; Zoovet Products, International Zoo Veterinary Group) and a nutritional supplement (Mazuri Exotic Feline; PM Nutrition International). A gradual clinical improvement was observed over the following six weeks. The animal's serum vitamin A concentration was 2.41 μmol/l six weeks after starting the vitamin supplementation, and 2.58 μmol/l after 36 weeks of supplementation. The serum vitamin E concentration, assessed six weeks after starting vitamin supplementation, was normal. A neurological examination carried out eight weeks after starting the vitamin A supplementation did not reveal any abnormalities. The serum vitamin A and E concentrations of the cheetah's dam were assessed when the cheetah was eight months old, and were within the normal ranges.
At approximately 13 months of age, the cheetah began to show signs of progressive visual impairment; it started bumping into static objects with increased frequency. The animal was otherwise neurologically normal until it suddenly became unable to stand up and walk following a possible traumatic event at 17 months of age. Three days after becoming non-ambulatory, the animal was presented at the Neurology-Neurosurgery Service for clinical examination and MRI. A neurological examination revealed non-ambulatory tetraparesis and normal mental status; the neuroanatomical localisation was to the C1 to C5 spinal cord segments. MRI of the cervical spine revealed extensive T2-weighted hyperintense changes at the level of the C3-C4 vertebrae within the paravertebral muscles, intervertebral foramina and surrounding the articular processes. Heterogeneous material dorsally within the vertebral canal disrupted the epidural fat signal and produced focal spinal cord compression with mild focal T2-weighted intramedullary hyperintensity. There was extensive enhancement of all affected tissues on postcontrast images. The changes were considered representative of widespread inflammation, a traumatic lesion or infection.
MRI of the brain (Fig 2) revealed a substantial change in skull conformation compared with the MRI performed 11 months previously. The exoccipital, basioccipital and basisphenoid bones and the tentorium cerebelli osseum had remodelled considerably and were no longer thickened. The cerebellar herniation and the flattening of the medulla oblongata had resolved.
Ophthalmic examination revealed normal pupillary light reflexes while the animal was conscious. Under general anaesthesia and pupillary dilation, a full fundus examination was undertaken, revealing bilaterally symmetrical generalised retinal atrophy with vascular attenuation and tapetal hyperreflectivity. An electroretinogram performed under general anaesthesia revealed a lack of retinal electrical response to light stimulation.
The cheetah did not respond to antibiotic and anti-inflammatory treatment and strict confinement for six days, and was humanely euthanased. Histological examination of the brain revealed focal disruption of normal cortical layering confined to the caudoventral aspects of the cerebellar vermis. On close examination, patchy loss of Purkinje cells, followed by moderate Bergmann's gliosis, thinning of the molecular layer and granular cell depletion, fibrillary astrogliosis and astrocytosis, and atrophy of the associated foliary white matter were noted. These chronic changes were interpreted as residuals of the prolonged cerebellar vermis compression that was diagnosed by MRI when the cheetah was six months old, which subsequently resolved after treatment. There was no postmortem evidence of caudal fossa overcrowding or cerebellar vermis compression.
The optic nerve, optic chiasm, optic tract, optic radiation, lateral geniculate body and visual cortex were macroscopically and histologically normal. Histology of the eye revealed severe degeneration and loss of retinal photoreceptors, a moderate drop-out of bipolar nerve cells and degeneration of ganglion cells.
Consistent with the history of probable trauma and the MRI findings, the cervical musculature at the C3-C4 vertebral segments showed laceration, haemorrhage, fibrous replacement and inflammatory changes. Via the fascia, interstitial tissue clefts and the tendinous attachments, the inflammation extended to the articular joint capsule and through the intervertebral foramen into the epidural space at C3-C4, where the tissue gain resulted in concentric compression of the spinal cord. Consequently, both the white and grey matter of the C3-C4 spinal cord segment showed degenerative features compatible with a compression myelopathy.
The caudal fossa overcrowding, resulting in compression of the adjacent nervous tissue, was the most likely cause of the neurological deficits detected in the cheetah at six months of age. The apparent mild depression and increased salivation (possibly associated with nausea) may have been related to the vestibular signs. The animal's progressive neurological deterioration during the four weeks before vitamin supplementation began, the lack of response to initial antibiotic and steroid treatment, and the gradual improvement that occurred following vitamin supplementation suggest that the supplementation resulted in the clinical improvement. The very low serum vitamin A concentration that was detected when the animal initially showed neurological signs, and the resolution of these signs when serum vitamin A returned to normal values, also supports a nutritional aetiology for the cheetah's neurological dysfunction. However, as the vitamin A was provided in a multivitamin and mineral complex, it is possible that multiple deficiencies were responsible for the neurological dysfunction.
The neurological deficits (progressive ataxia, impaired balance and nystagmus) and caudal fossa abnormalities observed in the cheetah are very similar to those reported in the early stages of disease in young captive lions diagnosed with hypovitaminosis A on the basis of liver vitamin A concentrations lower than that reported for a normal wild lion (Bartsch and others 1975, O'Sullivan and others 1977). Similar caudal fossa abnormalities and associated neurological deficits have been reported in young dogs, pigs, calves and birds with spontaneous or experimentally induced hypovitaminosis A (Mellanby 1941, Blakemore and others 1957, Howell and others 1967, Howell and Thompson 1970, Carrigan and others 1988). In these species and in the young captive lions the caudal fossa overcrowding was associated with obvious thickening of the caudal fossa bones. The degree of bone thickening was difficult to assess objectively in the cheetah, as the skull of an age-matched cheetah was not available for comparison and there is no information available on normal skull morphology in young or adult cheetahs. In comparison with CT images obtained of the only available anatomical reference specimen, that of the skull of a normal adult cheetah, subjective thickening of the exoccipital, basioccipital and basisphenoid bones and the tentorium cerebelli osseum, resulting in caudal fossa overcrowding and compression of adjacent nervous structures, were observed on the first MRI, carried out when the cheetah was six months old. The second MRI, performed 11 months later, revealed a decrease in the thickness of these bones and a substantial change in the caudal fossa morphology, with resolution of the compression of the adjacent nervous structures, as was confirmed by postmortem examination. This morphological change was likely to be due to bone remodelling following vitamin supplementation. Similar to the observations in this cheetah, a six-month followup MRI in a lion cub that showed complete clinical recovery after vitamin A supplementation revealed an improvement in the caudal fossa morphology (Hartley and others 2005), and vitamin A supplementation has been associated with clinical improvement in lion cubs with mild to moderate neurological dysfunction due to presumptive or confirmed hypovitaminosis A (Bartsch and others 1975, Hartley and others 2005).
It is likely that the hypovitaminosis A in the present case resulted from dietary deficiency, as the cheetah was fed lean red meat with no offal, and this type of diet has been implicated in vitamin A deficiency in lions (Bartsch and others 1975, O'Sullivan and others 1977). Felids require preformed vitamin A in their diet as they cannot convert β-carotene to retinol (Schweugert and others 2002). Circulating vitamin A concentrations appear to reflect the dietary levels of vitamin A in cheetahs (Crissey and others 2003).
This is the first report of resolution of neurological signs and caudal fossa overcrowding in a young captive cheetah with hypovitaminosis A following multivitamin and mineral supplementation. Nutritional aetiologies should be considered and investigated in captive-bred young cheetahs with progressive neurological dysfunction.
The authors thank A. Tropeano, Zoological Director of Colchester Zoo, J. C. M. Lewis and N. Masters (International Zoo Veterinary Group), and C. Hartley and J. Samson (Comparative Ophthalmology Unit, Animal Health Trust) for their contribution to the management and investigation of the cheetah.
Provenance not commissioned; externally peer reviewed
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