Familial Cerebellar Ataxia in the Bull Mastiff

The aim of this study was to provide information about the nature and incidence of cerebellar disease in dogs with specific reference to familial conditions. Investigative studies were carried out on six closely related Bull Mastiff pups which were showing signs of cerebellar damage. The clinical details of each pup were recorded. The salient features of the condition were those of cerebellar ataxia and a proprioceptive defect often accompanied by hypermetria. The affected animals also demonstrated signs of visual impairment and bizarre behavioural changes. In each case euthanasia was carried out as a result of continued deterioration and unresponsiveness to treatment. Pathological investigations were carried out on all six of the pups. The brain and selected samples of other tissues were obtained for histopathological examination. Two of the six cases were perfusion-fixed under general anaesthesia and positive pressure ventilation. Pathological changes were confined to the brains of the affected animals. A mild to moderate degree of hydrocephalus was present in each case. This was demonstrated in Case 2 by ventriculography. The hydrocephalus was communicating in nature. Specific changes were detected in the deep cerebellar nuclei, the lateral vestibular nuclei and the inferior colliculi in each case. The changes were bilaterally symmetrical and consisted of areas of vacuolation and axonal degeneration. Light microscopy studies suggested that both oligodendroglia and axons were showing abnormalities. The distribution of the changes suggested that one of the main pathological features was degeneration of the distal Purkinje cell axons. Electron microscopy confirmed that vacuolation was occuring in the distal extension of the oligodentroglia. Axonal degeneration was also studied and many axons with accumulations of organelles detected. An attempt was made to correlate clinical findings with the pathological changes observed, by reviewing the literature concerning cerebellar pathology and its resultant clinical effects. Disease processes and experimentally induced conditions were both considered. As a result, it was ascertained that the majority of the clinical signs exhibited could be ascribed to the observed pathology. Some changes, for instance, bizarre behavioural changes could not be satisfactorily explained and likewise no clinical signs attributable to the lesions in the inferior colliculi were determined. No specific pathological changes were found as a result of hydrocephalus but it was impossible to evaluate the significance of this clinically. Very similar pathological findings have been observed as a result of some metabolic disorders. In chronic thiamine deficiency both the nature of the pathology and the distribution were similar to that seen in the mastiffs, likewise similar changes are seen in isoniazid toxicity and in many cases of anoxic brain damage. This is taken as an indication that the affected cells in these areas have common metabolic requirements. The pups examined were all closely related. An indication was given that many more pups had been affected. The pedigrees of all of these animals were analysed and showed that the condition has in all probability an autosomal recessive pattern of inheritance. A source dog was detected through which all of the affected animals could have inherited the trait. This dog, however, is not likely to be the animal in which the trait has arisen. Familial ataxia in the Bull mastiff would therefore appear to be a neuronal, abiotrophy; that is, premature death of certain cell types as a result of a genetically determined metabolic abnormality and is inherited as an autosomal recessive trait