Abstract
The Sumatran Tiger (Panthera tigris sumatrae) is critically endangered due to habitat loss and poaching. The captive population of Sumatran tigers is subject to a carefully managed breeding strategy as part of a comprehensive conservation program. We report on two related litters of Sumatran tiger cubs with a congenital vestibular disorder characterized by ataxia, head tilt and rolling. Diagnostic elimination tests suggest damage due to in utero viral infection or hereditary factors. Given the close relationship between the sires of each affected litter and the high level of inbreeding in the Australasian population of Sumatran tigers, a genetic cause is likely. In order to define this disorder further, retrospective pedigree mapping and ongoing monitoring of all new cubs is needed.
Case Reports
A litter of three Sumatran tiger cubs (two males, one female) was born at Perth Zoo, Western Australia, as the result of the first breeding event of sire and dam. Early video footage of the cubs was of variable quality; however, keepers frequently commented on the “clumsiness” of the cubs. The cubs were first examined closely at the time of their primary vaccinations at 6 weeks of age. Cub 1, (the female) had noticeable ataxia, head tilt to the left and ventral strabismus of the left eye. Abnormal nystagmus was not evident, menace response was poor and visual response was considered reduced. Cub 2 appeared normal. Cub 3 had a mild head tilt to the right, but no other signs. Conscious radiographs of the heads of cubs 1 and 2 did not reveal any abnormalities.
A veterinary neurologist subsequently examined all three cubs. Cub 1 remained ataxic but had no discernable head tilt or strabismus. Cub 2 showed no abnormal signs. Cub 3 now showed marked ataxia and a dramatic right-sided head tilt. All cubs’ postural reactions and visual responses were considered normal. CBC and serum chemistry were run on all cubs. All three cubs had low PCV (0.26, 0.21 and 0.22 L/L, reference levels 0.371 L/L, SD 0.059),4 low RBC (4.4, 4.7x1012/L, reference levels 6.4x1012/L, SD 1.13)4 and low Hb (83, 71, 74 g/L, reference levels 124 g/L, SD 22)4. Serum biochemistry was unremarkable and Toxoplasma titers on cubs 1 and 2 were negative. Toxoplasma titers were not done on cub 3.
Over the next few months, the degree of ataxia and head tilt evident in cubs 1 and 3 varied from day to day. Ataxia and head tilting were more obvious when the cubs were lifted up and then put down. Cub 1 showed no evidence of vestibular disturbance by the age of 8 months as assessed by observation. Ataxia and head tilt of cub 3 had resolved by 5.5 months of age. Cub 2 remained unaffected. Investigation into the parents’ medical history revealed that the sire of this litter had suffered from similar clinical signs, which resolved by 5 months of age. In his case, a diagnosis of vestibular disease due to inflammation was reached based on a high percentage of macrophages in cerebrospinal fluid (CSF), though blood contamination was recorded.
A second litter of cubs (two males and one female) was born 3 years later at Taronga Zoo, Sydney, Australia, to different parents, though this was also their first pairing. The grand-dam on the father’s side was the littermate of Perth Zoo’s sire, though she showed no abnormal signs. Twenty-four hour closed-circuit television monitoring was available from the den and nest box areas. Within one day of an uneventful birth, all three cubs were showing unusual behavior. Each cub held its head twisted and flexed to one side. Deliberate progressive forward movement was uncoordinated, often resulting in repeated rolling to the side. The cubs’ righting response was poor, and they would often end up on their backs with their forelegs extended and paddling, and their heads twisted over their back. The cubs were otherwise strong, of normal size, and once attached to the teat they suckled well. Maternal care was excellent and the cubs’ growth rates were normal. Despite the adult diet ration having adequate thiamine, extra daily supplementation of the dam’s meat ration with 312 mg thiamine (Vitajek Vitamin B1, Jurox Pty. Ltd., Rutherford, NSW, Australia) was instituted for a period of 3 weeks. The cubs were examined briefly at 3 weeks of age. All still showed uncontrolled rolling and head tilting. Two cubs had their eyes open and had a mild bilateral ventral strabismus.
At 6 weeks of age, each cub was given a detailed examination by a veterinary neurologist. All cubs showed symmetric ataxia in all four limbs and would fall to either side and roll continuously. They had variable degrees of head tilt and showed wide side-to-side head movements as they moved forward. If held and lowered to the ground, they circled tightly. Pupillary responses were normal, menace responses poor and there was no abnormal strabismus or nystagmus. No other abnormalities were seen on cranial nerve examination, postural reactions were difficult to assess and spinal reflexes were not tested. Any vision and hearing deficits could not be determined, though subjective clinical assessment suggested the cubs could see and hear. CBC showed all cubs to have low PCV (0.24, 0.21, 0.28 L/L) compared to reference values.4 Serum chemistry was within normal limits. FeLV, FIV and paired Toxoplasma IgG titers were negative for two cubs. The third was not tested.
At 4 months of age, the cub with the most marked vestibular signs was anesthetized for a detailed physical examination, including ophthalmoscopic and otoscopic examinations. Findings were unremarkable. Magnetic resonance imaging (MRI) of the head did not reveal any abnormalities in the brain or middle and internal ear structures. CSF was normal, and no organisms grew on bacterial or fungal culture. Toxoplasma titers on CSF were negative. Feline coronavirus antibody titer was negative.
By 5 months of age, all the cubs remain in good health but still have intermittent and variable head tilts, and occasionally fall to one side or circle when changing direction or when distressed.
Discussion
Congenital vestibular disorders have been described in several breeds of domestic dogs and cats.1-3,7 An undiagnosed neurologic disease thought to be toxic or metabolic has been seen in successive litters of Sumatran tigers at London Zoo,8 but no reports were found involving congenital neurologic conditions in tigers.
Vestibular disease can be peripheral (affecting the semicircular canals or the vestibular nerve) or central (affecting the vestibular nuclei in the brainstem, the cerebellar peduncles or the flocculonodular lobe of the cerebellum). Clinical signs indicating central vestibular disturbance (paresis, cranial nerve abnormalities, altered mentation and postural reactions) were absent in the cubs although postural reactions were difficult to assess. Variable head tilt (not consistently to one side), symmetric ataxia and side-to-side sweeping head movements are characteristic of bilateral vestibular disease. It was determined from the neurologic examinations that affected cubs of both litters suffered from a congenital bilateral vestibular disorder with the precise location of any lesion undetermined.
Hearing deficits have been reported in domestic cats and dogs with congenital vestibular disease.2,7 Hearing deficits may be present in these cubs but have not been accurately assessed. A hearing deficit may be associated with a central abnormality, or abnormality of the cochlea, or cochlear nerve, which are closely associated with the semicircular canals and the vestibular nerves. It is difficult to accurately assess hearing by clinical examination. Any response to noise may be influenced by fear, cues from littermates, or inadvertent visual or olfactory cues. In order to assess hearing in the tiger cubs, a brainstem auditory evoked potential (BAEP) test is planned.
Vestibular signs in some affected animals appear to regress by about 5 months of age.1,7 Apparent clinical resolution may be attributable to central compensatory mechanisms rather than restored function of the vestibular apparatus. Redevelopment of signs in the few months following recovery is not uncommon. In domestic cats and dogs, where present, deafness is permanent.1,2,7
Trauma, vascular incident, neoplasia, immune-mediated inflammation, and otitis interna due to spread of bacteria from the middle ear (via the Eustachian tube or external ear canal) were ruled out as causes based on history, ancillary tests and the age and geographic separation of the two litters. Malformations, including middle and inner ear structural abnormalities and cerebellar hypoplasia, were not evident on MRI performed on one Taronga cub, and skull x-rays were normal in two of the Perth cubs.
Subacute thiamine deficiency can produce degeneration in the cerebellar and vestibular nuclei. In both affected litters, dietary thiamine intake of the dam was presumed to be adequate. The presence of signs from birth and the absence of response to additional thiamine supplementation of the dam at Taronga did not suggest thiamine deficiency as a likely cause.
A congenital viral or protozoan infection co-incident to both litters is possible. No infectious agents were isolated via cytologic analysis or bacterial and fungal culture of CSF on one cub. No attempt was made to culture mycoplasma. Negative Toxoplasma titers on five cubs did not support a diagnosis of toxoplasmosis. Both dams were in good health throughout their pregnancies. Both had current vaccination status for feline panleucopenia, feline rhinotracheitis and feline calicivirus, and neither received any toxic drugs or live virus vaccines. Two cubs tested negative for FIV and FeLV. There was no evidence of concurrent or multisystemic disease. All cubs of both litters were mildly anaemic. The cause of this was unknown but could represent iron deficiency common in milk-dependent animals. The anaemia had resolved within 3 weeks in two out of three cubs at Taronga Zoo.
All affected cubs are still alive, and no histopathology data is available. Pathologic examination of a litter of Doberman dogs with congenital vestibular disease revealed labyrinthitis, although no infectious agent was identified using ancillary tests.3
A genetic cause is highly likely given the close relationship between the sires of the two affected litters. The Australasian captive population of Sumatran tigers is derived from nine founders. Unequal contributions by the founders have added to a high rate of inbreeding. The distribution of known affected animals could fit with a single gene, autosomal recessive mode of inheritance. In order to determine the nature of a genetic cause for this disorder, a retrospective pedigree indicating affected animals should be compiled. This may prove difficult since mildly affected cubs may have been overlooked due to the practice of non-disturbance of cubbing female tigers to prevent mismothering, variation in severity of signs, and early compensation. There are numerous anecdotal references to tiger cubs with head turning and stargazing, which could be analogous with the syndrome reported here.6
The Australasian and European populations of Sumatran tigers are managed cooperatively. A potential genetic disease with clinically apparent signs, where permanent deafness may be present, represents a significant threat to a successful captive breeding program. As a precaution, consideration should be given to preventing affected tigers from breeding until the exact nature of the disease is known. Close monitoring of all future Sumatran tiger cubs along the following guidelines is suggested:
- All cubs should be monitored from birth by closed-circuit video.
- All cubs should receive a full neurologic exam co-incident with the first vaccination.
- Tissues/blood samples should be collected from all cubs and stored for future genetic work.
- All affected cubs should have hearing assessed by BAEP testing along with examination by a veterinary ophthalmologist to detect visual defects.
Acknowledgments
The authors wish to acknowledge the assistance of veterinary neurologists Georgina Child, BVSc, DACVIM (Neurology); Fiona Haining, BVMS, MVM; and David Pepper-Edwards, ASMP, Tiger Coordinator (Australasia).
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