Clinical Signs

In cheetah cubs and adults, onset of ataxia or paresis is usually peracute to acute and may occur spontaneously or after a stressful event for the individual or the litter. Events that have been described include hand capture, restraint, and transport for examination or treatment and translocation to a new enclosure. In cubs, clinical signs are often preceded by sneezing and ocular discharge typical of feline herpesvirus type 1 (FHV-1) infection in the dam or littermates.

Whereas clinical onset always starts with pelvic limb ataxia/paresis, disease progression and severity of the symptoms vary considerably among individuals. The clinical neurologic signs indicate an upper-motor-neuron lesion and proprioceptive deficits, with involvement of the long-tract sensory pathways in all cases. After onset of hind limb ataxia, sometimes with involvement of the forelimbs, simultaneous and subsequent recorded symptoms include paresis, staggering, knuckling, swaying high-stepping gait (hypermetria), falling over while turning, dragging of the paws or hind limbs, difficulty rising to a standing position, and finally, in the most severe cases, recumbency. In most cases these clinical symptoms are accompanied by slowly developing wasting (disuse atrophy) of the hind limb muscles. In the standing position the hind legs are typically placed more laterally than normal (abducted) in a base-wide stance, and support of the tail is reduced. In some cases, urinary incontinence was indicated by urine soiling of the perineum. Tremor of the head was observed in some advanced cases.

As previously stated, the course of the disease is variable; the initial ataxia and paresis may develop rapidly to hind limb paralysis and recumbency or may progress slowly and stabilize with mild symptoms for several months or years. Although clinical improvement after tentative treatment was observed in a few cases, relapsing bouts of ataxia or paresis eventually reappeared in most cases. Throughout the disease progression, the affected cheetahs had a normal appetite, did not seem to experience pain, remained alert, and responded to visual and auditory stimuli.^14,26,27,29

Epidemiology

To date, more than 60 cases have been recognized in at least 16 different institutions, including zoologic parks and private owners. The first cases of cheetah ataxia were described in South Africa in 1981,³ but since then, the syndrome has been reported only in Europe and the United Arab Emirates. Some anecdotal evidence from wild-caught cubs in Namibia has been reported.⁹ All affected cheetahs have been captive-bred in a European, Middle Eastern, or South African institutions from captive-borne or wild-caught parents, belonging to the South African subspecies (Acinonyx jubatus jubatus) or East African subspecies (Acinonyx jubatus soemmeringii). All affected cheetahs were born from parents without prior clinical neurologic signs. Some of the parents were known to have produced other healthy litters before or after the ataxic litters, and individual parents developed ataxia themselves at a later stage. Often, several or all cubs or siblings from a same litter were affected, with symptoms starting simultaneously in all individuals or developing successively over several months or years. There is no apparent gender predilection, and the age of onset of the ataxia ranges from 2.5 months to 12 years.

The captive management and holding conditions vary among institutions that have reported ataxic cheetahs, and no “common denominator” could be identified to date. At most facilities, the cheetahs live in enclosures of varying size with natural soil, usually grassy areas, and heated indoor pens. Ataxia has been recorded at institutions keeping only one pair of animals, as well as institutions holding several cheetahs together or in separated paddocks, usually adjacent to each other. In most institutions the cheetahs are housed in visual or auditory range of unrelated cheetahs or other species. Feeding regimen is mostly composed of a daily meat ration (rabbit, goat, chicken, calf), usually supplemented with a vitamin-mineral additive. In a few institutions the meat is attached to a ski lift–like mechanism that provides a simulated hunting situation, encouraging frequent physical exercise.

Vaccination and deworming of the young and adult cheetahs are routine in all institutions that have reported ataxic animals. A few cubs developed clinical signs before vaccination, but most of the affected cheetahs were routinely vaccinated against feline parvovirus (FPV), FHV-1, and feline coronavirus (FCV) using inactivated or modified live vaccines.^14,26,29 Some individuals were also vaccinated against feline leukemia virus (FeLV). Known products used for deworming include ivermectin, mebendazole, fenbendazole, febantel, pyrantel pamoate for cubs, pyrantel tartrate, and fipronil.

Clinical Pathology and Ancillary Procedures

Thorough clinical investigations have been carried out in most reported ataxia cases. Although the cheetah myelopathy has often been temporally associated with clinical herpesvirus infection in cubs, no definitive etiologic factor could be determined.^14,26,27,29 Plain radiographs, contrast myelography, and magnetic resonance imaging (MRI) were normal. No abnormalities were detected in the cerebrospinal fluid (CSF) or in the urine.

Hematology and blood chemistry values were always within the normal range. Serum copper values (6-22 μmol/L) revealed no significant difference between ataxic cheetahs and domestic dogs and cats. Furthermore, there was no significant difference in liver copper levels between ataxic cheetahs (4.6 ±3 ppm) and cheetahs without CNS disease (4.3 ±1.5 ppm). However, a significant difference in liver copper has been shown between cheetahs and dogs and cats, but not a wild lynx.²⁹ This difference might be explained by the domestic animals being mostly fed with supplemented commercial food.

Serologic examinations revealed negative or low titers against feline infectious peritonitis (FIP), canine distemper virus (CDV), FPV, FCV, FeLV, feline immunodeficiency virus (FIV), Borna disease virus (BDV), encephalomyocarditis virus, tick-borne encephalitis virus, mucosal disease complex virus, Teschen-Talfan disease virus, Listeria monocytogenes, and Chlamydophila psittaci. Antibody titers against FHV-1 and Toxoplasma gondii were elevated in several cases but negative in another institution, although the cubs had shown ocular discharge and mucopurulent conjunctivitis.¹⁴ The tests for FIP were also negative.²⁶

A herpesvirus was isolated from the eyes and nose of one cub with ocular discharge, and the gene sequence showed 99% overlap with FHV-1.²⁹

At necropsy, ataxic cheetahs are frequently diagnosed with mostly mild or moderate lesions in non-CNS organs. Most of these non-CNS diseases are “classic” diseases frequently observed in captive cheetahs, such as gastritis, enterocolitis, glomerulosclerosis or glomerulonephritis, hepatic or renal amyloidosis, and myelolipoma. However, no correlation could be made with the myelopathy.

Pathology

Gross pathologic lesions in the spinal cord are rarely seen and consist of multifocal, segmental, bilateral, symmetric, grayish white discoloration of the spinal cord white matter.

Histologically, almost exclusively the white matter of the spinal cord is affected in all animals, consisting of continuous columns of white matter degeneration with only occasional presence of chromatolytic neurons in the gray matter. The lesions of the spinocerebellar tracts (laterodorsal funiculi) may extend into the medulla oblongata up the cerebellar peduncles. Discrete perivascular lymphocytic infiltration may be observed in the brainstem and the spinal cord meninges. In the ventral roots, dorsal roots, and peripheral nerves, rare wallerian degeneration with typical digesting chambers has been noted, as well as occasional chromatolytic neurons in the dorsal root ganglia. Neuronal lipofuscinosis is regularly seen in the brain and spinal cord gray matter in animals older than 6 years. No other lesions are observed in the white and gray matter of the brain.

The pattern, distribution, and severity of histologic lesions vary among individuals. Lesions are most prominent from the distal cervical to midthoracic segments, gradually decreasing in severity toward the craniocaudal direction. The degenerative changes are always bilaterally symmetric and often affect the entire circumferential length of lateral and ventral spinal cord funiculi, involving both ascending and descending tracts. The proper fascicle usually is largely spared, and the dorsal tracts are affected only in a few cases, generally older animals. The degenerative lesions are characterized by ballooning of myelin sheaths, either devoid of axons or containing intact or fragmented axons or macrophages (gitter cells, myelinophages). On the longitudinal sections, intact or slightly swollen axons are often seen within dilated myelin sheaths. Spheroids are observed rarely. Depending on the severity and duration of the lesions, myelin sheath vacuolation is associated with varying degrees of astrogliosis, characterized by gemistocytes and proliferation of fibrous processes. Considering the presence of intact axons within dilated myelin sheaths, the lack of features typical for early axonal degeneration, and the excess of myelin loss compared with axonal degeneration, the white matter lesion has been classified as a primary myelin disorder.^26,29 However, based on ultrastructural studies, other authors suggest that demyelination must be considered secondary to axonal degeneration.¹⁴