Cerebellar cortical abiotrophy in two Portuguese Podenco littermates

Cerebellar cortical abiotrophy in two Portuguese Podenco littermates is reported and discussed. The disease is characterized by progressive cerebellar ataxia with an early onset of two to three weeks. Extensive loss, degeneration, and necrosis of Purkinje cells particularly involved the cerebellar hemispheres. An autosomal recessive pattern of inheritance is suspected.     

Cerebellar cortical abiotrophy in American Staffordshire terriers: clinical and pathological description of 3 cases

Three American Staffordshire Terriers were presented with gait abnormalities and loss of balance at the age of 4.5 (female) and 6 years (2 males). The onset varied between 3 and 5 years of age and the clinical signs were slowly progressive. The neurological examination revealed symmetrical generalized cerebellar ataxia with hypermetria, stiffness, and loss of balance with no evidence of paresis. The menace reflex was decreased in one dog and absent in another. A positional nystagmus was found in two dogs. The dogs were euthanized and a histopathological examination of each brain was performed. Pathological changes were confined to the cerebellum. The main finding was loss of Purkinje cells, as well as depletion of granular cell bodies and shrinkage of the granular and molecular cell layer. These findings are consistent with cerebellar cortical abiotrophy. A genetic basis is supposed, but the mode of inheritance is not determined yet. In contrast to some spinocerebellar ataxias in humans, the cause of Purkinje cell degeneration in cerebellar cortical abiotrophy of dogs is not known.     

Cerebellar cortical abiotrophy in Wiltshire sheep

AIM: To investigate the nature of a neurological disease in Wiltshire sheep. METHODS: Three affected lambs were examined, humanely killed and necropsied. Selected neurological tissues were examined by light and electron microscopy. RESULTS: Primary neurological lesions were confined to the cerebellum and were characterised by loss of Purkinje cells and the presence of large hypertrophied dendrites of surviving Purkinje cells. These contained stacks of smooth endoplasmic reticulum. There was hyperplasia and cell swelling of Bergmann glia. Mild Wallerian-type degeneration affected white matter in the cerebellum and spinal cord. CONCLUSION: The cerebellar lesions were of a degenerative and reactive rather than hypoplastic nature. These, and the history, suggest a genetic cause with putative inheritance as an autosomal recessive trait. Accordingly, the disorder is described as a cerebellar abiotrophy.     

Cerebellar granuloprival degeneration in an Australian kelpie and a Labrador retriever dog

A 7-month-old Australian kelpie dog and a 14-month-old Labrador retriever dog were diagnosed with an uncommon form of cerebellar abiotrophy called cerebellar granuloprival degeneration. This was characterized by a loss of the granular neurons with relative sparing of the Purkinje neurons.     

Cerebellar cortical abiotrophy in Wiltshire sheep

AIM: To investigate the nature of a neurological disease in Wiltshire sheep.

METHODS: Three affected lambs were examined, humanely killed and necropsied. Selected neurological tissues were examined by light and electron microscopy.

RESULTS: Primary neurological lesions were confined to the cerebellum and were characterised by loss of Purkinje cells and the presence of large hypertrophied dendrites of surviving Purkinje cells. These contained stacks of smooth endoplasmic reticulum. There was hyperplasia and cell swelling of Bergmann glia. Mild Wallerian-type degeneration affected white matter in the cerebellum and spinal cord.

CONCLUSION: The cerebellar lesions were of a degenerative and reactive rather than hypoplastic nature. These, and the history, suggest a genetic cause with putative inheritance as an autosomal recessive trait. Accordingly, the disorder is described as a cerebellar abiotrophy.     

Morphometric analysis of progressive changes in hereditary cerebellar cortical degenerative disease (abiotrophy) in rabbits caused by abnormal synaptogenesis

We previously investigated rabbit hereditary cerebellar cortical degenerative disease, called cerebellar cortical abiotrophy in the veterinary field, and determined that the pathogenesis of this disease is the result of failed synaptogenesis between parallel fibers and Purkinje cells. In this study, longitudinal changes in the development and atrophy of the cerebellum of rabbits with hereditary abiotrophy after birth were morphometrically examined (postnatal day [PD] 15 and 42) using image analysis. Although development of the cerebellum in rabbits with abiotrophy was observed from PD 15 to PD 42, the growth rate of the cerebellum was less than that in normal rabbits. In rabbits with abiotrophy, the number of granular cells undergoing apoptosis was significantly higher at PD 15 and dramatically decreased at PD 42. The number of granular cells did not increase from PD 15 to 42. The synaptogenesis peak at PD 15 occurred when the largest number of apoptotic granular cells in rabbits with abiotrophy was observed. Although 26% to 36% of parallel fiber terminals formed synaptic junctions with Purkinje cell spines, the remainder did not at PD 15 and 42. The rate of failure of synaptogenesis in the present study might be specific to this case of abiotrophy. Morphometric analysis revealed detailed changes in development and atrophy in animals with postnatal cerebellar disease occurring soon after birth.     

Cerebellar abiotrophy in a 6‐year‐old Arabian mare

Cerebellar abiotrophy (CA) is an uncommon neurological disease that most commonly affects Arabian horses. Affected horses are typically identified within the first 6 months of life. Intention tremor, wide based stance and ataxia are common clinical signs observed in affected individuals. No treatment is available for resolution of clinical signs. Definitive diagnosis is based on histopathological examination of cerebellar tissue, which is characterised by loss of Purkinje cell layer. This report describes a case of cerebellar abiotrophy that had a delayed diagnosis until 6 years of age.     

Cerebellar cortical abiotrophy in Lagotto Romagnolo dogs

This case report documents two pathological variations of potentially inherited, cerebellar cortical abiotrophy in two unrelated Lagotto Romagnolo breed dogs. The first dog had an atypical lesion in the cerebellar cortex with depletion of cerebellar granular cell layer and sparing of the Purkinje cell layer. The second case had degenerative changes in both Purkinje and granular cell layers. The clinical picture was similar in both cases presented, although the severity of the signs of cerebellar dysfunction varied.     

Cerebellar abiotrophy and segmental axonopathy: two syndromes of progressive ataxia of Merino sheep

Findings of a study of 39 sheep with progressive ataxia from 14 farms in the Yass district of New South Wales are described. Microscopic lesions in 25 sheep, 3.5 to 6 years of age, diagnosed as having clinical cerebellar disease, consisted of an apparent primary loss of cerebellar Purkinje neurons, and glial cell accumulation. It is suggested that this previously unreported disorder may be an hereditary cerebellar abiotrophy of Merino sheep. A further 14 sheep, 1 to 4 years of age, had distinguishable clinical signs referable to a spinal cord lesion with widespread segmental axonal ballooning, or "spheroids", in the white matter of the brain and spinal cord. It is suggested that these sheep have a unique form of neuroaxonal dystrophy, described here as segmental axonopathy, and that this is likely to be the same condition described previously as Murrurindi disease (Hartley and Loomis 1981).     

Cerebellar granuloprival degeneration in an Italian hound

A severe atrophy of the cerebellum was observed in a 7-month-old male Italian hound with a history of progressive ataxia and head tremor from the age of 3 months. On clinical examination, signs included severe hypermetric gait, head tremors and proprioception deficits in all limbs. At necropsy, a pronounced symmetrical reduction in size of the cerebellum was the only gross lesion observed. Histological examination of the cerebellum revealed marked thinning of the granular and molecular layers with almost complete loss of granule cells. Purkinje cells had normal morphology and distribution. These findings differ from those of previous reports of cerebellar cortical abiotrophy in dogs, which were mainly characterized by prominent Purkinje cell degeneration and loss.     

Cerebellar abiotrophy in crossbred cattle

Cerebellar abiotrophy affected 9 of 74 calves sired by a Poll Hereford bull over 2 successive calving seasons. The disease was characterised by episodes of recumbency and ataxia, with hypermetria and wide base stance. Clinical signs commenced between birth and 8 months of age. Two calves which were affected first at 8 months of age recovered clinically 9 months later. Histological lesions were found in the cerebellar cortex of 7 calves and consisted of segmental degeneration and loss of Purkinje cells, and axonal swellings. The clinical signs and pathological findings were consistent with bovine familial convulsions and ataxia, which has not been described previously in Australia. The clinical signs were not attributable to the lesions observed in the cerebellum and an underlying electrophysiological abnormality is proposed. The aetiology of the condition is probably genetic and appears to have a multifactorial basis.     

Hereditary cerebellar degeneration in three full sibling kittens

Two domestic shorthair littermate kittens had signs of cerebellar dysfunction, first observed between seven and eight weeks of age; a third littermate was unaffected. The signs were progressive and the more severely affected kitten was euthanased after six days. A postmortem examination revealed no gross lesions but the kitten had cerebellar cortical degeneration with extensive loss of Purkinje cells. The second kitten was euthanased at 10 months of age with similar, though more pronounced, changes. One of the two kittens in the next litter of the same parents had similar clinical signs and histopathological findings. The lesions in the cerebellum are interpreted as probably due to genetically determined abiotrophy. In addition, the two older kittens had medullary neuronal changes interpreted as probable neuraxonal dystrophy, and focal vacuolation of the neuropil in the medulla and cervical spinal cord.     

Hereditary cerebellar degenerative disease (cerebellar cortical abiotrophy) in rabbits

A pair of rabbits gave birth to a set of littermates (F1) with symptoms of early-onset ataxia. Microscopic examination revealed cerebellar degenerative disease in 5 of 6 littermates. Light microscopy was used to compare the thickness of each cerebellar layer in affected animals in contrast to a normal control. Affected animals showed narrowing of the molecular layer of the vermis, reduced density of Purkinje cell dendrites and irregular thickness in their branchlets, and reduced density of granular cells and scattered pyknotic cells in the granular layer. Pyknotic cells were apoptotic granular cells, confirmed by positive staining using the TUNEL method. Electron microscopy confirmed the thinning of the molecular layer seen by light microscopy and also showed a reduced number of parallel fibers, which indicate granular cells axons, and a reduced number of synaptic junctions between Purkinje and granular cells. Purkinje cells had electron-dense, irregularly shaped cytoplasm with irregularly shaped nuclei, and some of these cells had a central chromatolysis-like region. These findings support a diagnosis of cerebellar cortical abiotrophy, a hereditary condition that causes nerve function impairment leading to early-onset progressive degeneration of the cerebellar cortex.     

Clinicopathological features of canine neuroaxonal dystrophy and cerebellar cortical abiotrophy in Papillon and Papillon-related dogs

Neuroaxonal dystrophy (NAD) was examined in two Papillon dogs and a mix breed dog between Papillon and Chihuahua. In addition, cerebellar cortical abiotrophy (CCA) in a Papillon dog, which had similar clinical and magnetic resonance imaging (MRI) features to those of NAD, was also investigated. The common clinical symptoms of all dogs affected with NAD and CCA, were pelvic limb ataxia and cerebellar ataxia including intention tremor, head tremor, and hypermetria in the early onset. These clinical signs were progressed rapidly, and two dogs with NAD were euthanized by owner's request and the other two died by aspiration pneumonia. MRI examinations and gross observations at necropsy revealed moderate to severe cerebellar atrophy in all cases of NAD and CCA. The most typical histological change of NAD was severe axonal degeneration with marked spheroid-formation in the dorsal horn of the spinal cords, the nuclei gracilis, cuneatus, olivalis and its circumference in the medulla oblongata. The spheroids were characterized as large eosinophilic or granular globes within the enlarged myelin sheaths, sometimes accompanied by moderate accumulation of microglias and/or macrophages. In contrast, such spheroid formation was minimal in the brain of CCA. In the cerebellum, mild to moderate loss of the Purkinje and granular cells were recognized in three dogs with NAD, whereas these changes were more prominent in a dog with CCA. Although the clinical signs and MRI findings relatively resembled between NAD and CCA, the histopathological features considered to be quite differ, suggesting distinct pathogenesis and etiology. Since both NAD and CCA are proposed as the autosomal recessive hereditary disorders, careful considerations might be needed for the breeding of Papillon and Chihuahua dogs.     

Cerebellar cortical abiotrophy in a beagle

A beagle puppy was presented with clinical signs indicative of a cerebellar disease. Histopathological evaluation of the cerebellum revealed a diffuse degenerative cortical lesion. The clinical history and the histopathological findings are consistent with a neonatal cerebellar abiotrophy. Furthermore, the breeding history supports the hypothesis of an inherited genetic disorder that is, most likely, an autosomal recessive trait.     

Diagnosis of cerebellar cortical degeneration in a Scottish terrier using magnetic resonance imaging

Primary cerebellar cortical degeneration (CCD), also termed abiotrophy, is the spontaneous premature degeneration of fully differentiated neurological tissue. Cerebellar hypoplasia shares many morphological features with primary CCD, both conditions being characterised by decreased cerebellar size, with reduced numbers of Purkinje and granular cells. CCD has been identified in many canine breeds. This is the first report of the syndrome in a Scottish terrier. The patient presented with mild, gradually progressive ataxia. Survey radiographs of the cervical spine and cerebrospinal fluid (CSF) analysis were normal. CSF distemper and Toxoplasma titres were negative. A diagnosis of cerebellar atrophy was made based on magnetic resonance imaging. The progressive clinical signs suggested cerebellar degeneration rather than hypoplasia. On necropsy, the cerebellum showed macroscopic and microscopic changes consistent with primary CCD.     

Cerebellar abiotrophy in a miniature schnauzer

A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer.     

A cerebellar abiotrophy of calves.

A postnatal cerebellar atazia of a type not previously reported in calves is described. Atazia was first noticed in affected animals when they were three to eight months of age, and was often accompanied by loss of the menace response in an animal which was not blind. The disorder was progressive. At postmortem cerebellar size was normal. Microscopic lesions consisted of primarily an apparent degeneration of cerebellar neurons without obvious evidence of inflammation. History, clinical signs, laboratory examination, gross pathology, histopathology, differential diagnosis, search for an etiologic agent and genetic histories are reported. It is concluded that this disorder may represent an hereditary cerebellar abiotrophy in Holstein cattle.     

Late onset cerebellar degeneration in a middle-aged cat

Cerebellar degeneration (abiotrophy) (CD) is a spontaneous and accelerated degeneration of one or several mature cerebellar neuronal cell populations and has been described in many domestic animals, especially in dogs, with numerous breed-related cases. In cats, CD is mentioned as a rare sporadic entity. Late onset CDs are exceptionally uncommon and only two cases are reported in young adults, both aged 18 months. This report describes clinical and pathological findings of a late onset feline CD in a 9-year-old male Persian cat. The cat was presented with a history of progressive ataxia lasting 2 years. Neurological examination revealed severe neurological deficits such as generalised and severe ataxia, hypermetria in all four limbs, and bilateral absence of menace response. The lesion was diffusely localised in cerebellum. On gross pathology, the cerebellum appeared of normal size and shape and kidneys were characterised by mild hyperaemia. Histologically, lesions were limited to the cerebellum and kidneys. In the cerebellum, all cerebellar folia of both hemispheres and the vermis were affected. Changes were characterised by severe and diffuse loss of Purkinje cells, loss of cellularity in the granular layer, mild astrogliosis associated with moderate hypertrophy of Bergmann's glia. Immunohistochemistry for feline parvovirus antigen revealed a negative result. Renal lesions consisted of chronic fibrosis associated with chronic interstitial nephritis. CD is a rare disease and occurs commonly in puppies or young animals, who are clinically normal at birth and usually develop neurological signs within a few weeks or months after birth. This report represents the first case of CD in a middle-aged cat.     

Cerebellar cortical degeneration with selective granule cell loss in Bavarian mountain dogs

Three Bavarian mountain dogs aged between 18 and 20 months, not related to each other, were presented with chronic signs of cerebellar dysfunction. On sagittal T2-weighted magnetic resonance imaging brain images, the tentative diagnosis of cerebellar hypoplasia was established based on an enlarged cerebrospinal fluid space around the cerebellum and an increased cerebrospinal fluid signal between the folia. Post-mortem examination was performed in one dog and did show an overall reduction of cerebellar size. On histopathologic examination, a selective loss of cerebellar granule cells with sparing of Purkinje cells was evident. Therefore, the Bavarian mountain dog is a breed where cerebellar cortical degeneration caused by the rather exceptional selective granule cell loss can be seen as cause of chronic, slowly progressive cerebellar dysfunction starting at an age of several months.