Mapping of Purkinje neuron loss and polyglucosan body accumulation in hereditary cerebellar degeneration in Scottish terriers

A hereditary cerebellar degenerative disorder has emerged in Scottish Terriers. The aims of this study were to describe and quantify polyglucosan body accumulation and quantify Purkinje neurons in the cerebellum of affected and control dogs. The brains of 6 affected Scottish Terriers ranging in age from 8 to 15 years and 8 age-matched control dogs were examined histopathologically. Counts of Purkinje neurons and polyglucosan bodies were performed in control and affected dogs on cerebellar sections stained with periodic acid-Schiff. Affected dogs showed a significant loss of Purkinje neurons compared with control dogs (vermis: P < .0001; hemisphere: P = .0104). The degeneration was significantly more pronounced dorsally than ventrally (P < .0001). There were significantly more polyglucosan bodies in the ventral half of the vermis when compared with the dorsal half (P < .0001) in affected dogs. In addition, there were more polyglucosan bodies in the ventral half of the vermis in affected dogs than in control dogs (P = .0005). Polyglucosan bodies in all affected dogs stained positively with toluidine blue and alcian blue. Immunohistochemically, polyglucosan bodies in affected dogs were positive for neurofilament 200 kD and ubiquitin and negative for glial fibrillary acidic protein, synaptophysin, neurospecific enolase, vimentin, and S100; the bodies were negative for all antigens in control dogs. Ultrastructurally, polyglucosan bodies in 1 affected dog were non-membrane-bound, amorphous structures with a dense core. This study demonstrates significant Purkinje cell loss and increased polyglucosan bodies in the cerebellum of affected Scottish Terriers.     

MAGNETIC RESONANCE IMAGING FINDINGS OF PRESUMED CEREBELLAR CEREBROVASCULAR ACCIDENT IN TWELVE DOGS

The magnetic resonance imaging (MRI) findings of presumed cerebrovascular accident in 12 dogs are described. Fourteen lesions were seen, commonly (11 of 14) within the gray matter of the cerebellar hemispheres or vermis. Thirteen lesions were hyperintense on T2-weighted images (in 11 dogs) and one was hypointense. Eleven of 14 lesions were within the region supplied by the rostral cerebellar artery or one of its main branches and there was no, or minimal, mass effect. Contrast enhancement was only seen in six lesions and was mild in all. Gradient-echo images provided additional information in two dogs. The appearance of infarction in dogs with diffusion-weighted images (DWI) is similar to that in humans, and provided supportive evidence for the diagnosis of infarction in five dogs. The use of gradient-echo and DWI is recommended for the evaluation of suspected cerebrovascular accidents in dogs. Six of the 12 affected animals were spaniels or spaniel crosses, suggesting a possible breed predisposition.     

Presentation,clinical pathological and post‐mortem findings in three related Scottish terriers with ligneous membranitis

Ligneous conjunctivitis and gingivitis were diagnosed in three related Scottish terrier dogs presented for investigation of severe conjunctivitis and respiratory signs. Hypoplasminogenaemia was confirmed in one of the three affected dogs. Supportive treatment was not effective, and the dogs died or were euthanased because of the disease. Post‐mortem analysis of two of the dogs revealed multiple abnormalities including severe proliferative fibrinous lesions affecting the conjunctiva, gingiva, trachea, larynx and epicardium and multiple fibrous adhesions throughout the thoracic and abdominal cavities. One dog had internal hydrocephalus and lacked a cerebellar vermis. Ligneous membranitis was confirmed on histopathology. This is a rare condition in dogs but an important differential diagnosis for severe conjunctivitis and gingivitis.     

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.     

Polymerase chain reaction (PCR) amplification of parvoviral DNA from the brains of dogs and cats with cerebellar hypoplasia

Cerebellar hypoplasia in cats is caused most commonly by an in utero or perinatal infection with feline panleukopenia virus (parvovirus). Cerebellar hypoplasia has been reported infrequently in dogs, but no viral etiology has been identified to date. DNA was extracted from archival, paraffin-embedded, cerebellar tissue from 8 cats and from 2 canine littermates with cerebellar hypoplasia, 2 canine littermates with cerebellar cortical abiotrophy, 6 dogs with congenital cerebellar vermal defects, 1 dog with congenital hydranencephaly, and 15 dogs and cats with various encephalitdes. The DNA extracted from each cerebellum was subject to polymerase chain reaction (PCR) amplification by 3 primer pairs specific for parvovirus DNA. Sequence analysis of PCR products from each of the 8 cats and 2 dogs with cerebellar hypoplasia confirmed their identity with parvoviral DNA. The 6 dogs with cerebellar vermal defects, 2 dogs with cortical abiotrophy, 1 dog with congenital hydranencephaly, and all control samples were PCR negative for parvovirus. Parvoviral structural proteins were not identified by immunohistochemistry in either dog with cerebellar hypoplasia. This study shows that parvoviral DNA can be amplified from feline and canine archival brain tissue and that cerebellar hypoplasia in dogs might be associated with in utero parvovirus infection.     

MAGNETIC RESONANCE IMAGING CHARACTERISTICS IN FOUR DOGS WITH CENTRAL NERVOUS SYSTEM NEOSPOROSIS

Neosporosis is a polysystemic disease that can affect dogs of any age and can cause inflammation of the central nervous system. Antemortem diagnosis can be challenging, as clinical and conventional laboratory test findings are often nonspecific. A previous report described cerebellar lesions in brain MRI studies of seven dogs and proposed that these may be characteristic for central nervous system Neosporosis. The purpose of this retrospective study was to describe MRI characteristics in another group of dogs with confirmed central nervous system neosporosis and compare them with the previous report. The hospital's database was searched for dogs with confirmed central nervous system neosporosis and four observers recorded findings from each dog's MRI studies. A total of four dogs met inclusion criteria. Neurologic examination was indicative of a forebrain and cerebellar lesion in dog 2 and multifocal central nervous system disease in dogs 1, 3, and 4. Magnetic resonance imaging showed mild bilateral and symmetrical cerebellar atrophy in three of four dogs (dogs 2, 3, 4), intramedullary spinal cord changes in two dogs (dogs 3, 4) and a mesencephalic and metencephalic lesion in one dog (dog 2). Multifocal brain lesions were recognized in two dogs (dogs 1, 4) and were present in the thalamus, lentiform nucleus, centrum semiovale, internal capsule, brainstem and cortical gray matter of the frontal, parietal or temporal lobe. Findings indicated that central nervous system neosporosis may be characterized by multifocal MRI lesions as well as cerebellar involvement in dogs.     

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.     

DEVELOPMENT OF A MORPHOMETRIC MAGNETIC RESONANCE IMAGE PARAMETER SUITABLE FOR DISTINGUISHING BETWEEN NORMAL DOGS AND DOGS WITH CEREBELLAR ATROPHY

Neurodegenerative diseases affect the cerebellum of numerous dog breeds. Although subjective, magnetic resonance (MR) imaging has been used to detect cerebellar atrophy in these diseases, but there are few data available on the normal size range of the cerebellum relative to other brain regions. The purpose of this study was to determine whether the size of the cerebellum maintains a consistent ratio with other brain regions in different ages and breeds of normal dogs and to define a measurement that can be used to identify cerebellar atrophy on MR images. Images from 52 normal and 13 dogs with cerebellar degenerative diseases were obtained. Volume and mid‐sagittal cross‐sectional area of the forebrain, brainstem, and cerebellum were calculated for each normal dog and compared between different breeds and ages as absolute and relative values. The ratio of the cerebellum to total brain and of the brainstem to cerebellum mid‐sagittal cross‐sectional area was compared between normal and affected dogs and the sensitivity and specificity of these ratios at distinguishing normal from affected dogs was calculated. The percentage of the brain occupied by the cerebellum in diverse dog breeds between 1 and 5 years of age was not significantly different, and cerebellar size did not change with increasing age. Using a cut off of 89%, the ratio between the brainstem and cerebellum mid‐sagittal cross‐sectional area could be used successfully to differentiate affected from unaffected dogs with a sensitivity and specificity of 100%, making this ratio an effective tool for identifying cerebellar atrophy on MR images.     

Computer-assisted magnetic resonance imaging brain morphometry in American Staffordshire Terriers with cerebellar cortical degeneration

BACKGROUND: Cerebellar cortical degeneration exists in American Staffordshire Terriers. Magnetic resonance imaging (MRI) can be suggestive, but a definitive diagnosis requires histopathology. HYPOTHESIS: Computer-assisted MRI morphometry can be used to distinguish between American Staffordshire Terriers with or without cerebellar cortical degeneration. ANIMALS: Normal American Staffordshire Terriers (n = 17) and those with clinical signs of cerebellar cortical degeneration (n = 14). METHODS: This was a partly retrospective and partly prospective study. Causes of cerebellar disease were ruled out with brain MRI, cerebrospinal fluid (CSF) analysis, CBC, blood biochemistry, and clinical follow-up. On T2-weighted midsagittal MR images, the following parameters were calculated: size of the cerebellum relative to the entire brain, size of the CSF space surrounding the cerebellum relative to the cerebellum, and 2 threshold-dependent cerebellar CSF indices (with and without surrounding CSF). RESULTS: Statistical analyses indicated a significantly lower relative cerebellar size (P < .001) and a larger relative cerebellar CSF space (P < .001) in dogs with cerebellar cortical degeneration. The measurement of relative cerebellar size could distinguish between affected and nonaffected dogs with a sensitivity and a specificity of 93 and 94%, respectively, using a cut-off of 13.3%. Using a cut-off of 12.8%, the measurement of relative CSF space could distinguish between both groups with a sensitivity of 93% and a specificity of 100%. There was a significant difference in 1 of the 2 CSF indices between affected and normal dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Relative cerebellar size and relative CSF space calculated from MRI are effective in American Staffordshire Terriers to differentiate between normal animals and those with cerebellar cortical degeneration.     

Computed tomography diagnosis of eight dogs with brain infarction

Objective Medical records of eight dogs presenting with acute onset of neurological signs and a diagnosis of brain infarction as determined by computed tomography (CT) imaging were reviewed. Design Retrospective single-centre case review Results Ischaemic infarction in the territory of the rostral cerebellar artery was identified in three spaniel-breed dogs. All cerebellar infarcts were non-haemorrhagic. Telencephalic infarcts were identified in five dogs, in the territories of the middle cerebral artery (2/5) and rostral cerebral artery (3/5). One of these dogs had an ischaemic infarction, but all other infarctions appeared haemorrhagic. All dogs were geriatric (≥8 years old), with concurrent medical conditions identified in six dogs. One dog was euthanased after diagnosis because of the severity of its neurological signs and one dog was euthanased as a result of associated renal disease 2 months after diagnosis. Six dogs were alive at least 1 year after diagnosis. Conclusions CT is useful in the diagnosis of cerebrovascular accident in dogs, which can present as a spectrum of images with early changes in attenuation and subtle mass effects detected after infarction. CT is particularly sensitive for detecting haemorrhagic infarction, but under-represent ischaemic and lacunar infarctions when compared with MRI.     

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.     

IMAGING DIAGNOSIS—SPLIT CORD MALFORMATION

The features of a calf with a split cord malformation are described. Clinically, there was severe cervicothoracic kyphoscoliosis and an interscapular dermal sinus associated with cerebrospinal fluid drainage. Using magnetic resonance imaging, complete duplication of the spinal cord at the cervical intumescence was detected. There was associated syringohydromyelia, multiple cervicothoracic vertebral malformations resulting in kyphoscoliosis and rachischisis, herniation of the cerebellar vermis, meningoencephalocele, and calvarial defects.     

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.     

Medulloblastoma in a cat: clinical and MRI findings

A two-year-old, castrated crossbred cat presented with loss of balance and anorexia. A mass of the caudal aspect of the cerebellum was revealed by magnetic resonance imaging (MRI). The mass was hypointense on T1-weighted images, iso- and hyperintense on T2-weighted images and was enhanced by intravenous gadolinium contrast medium. The MRI characteristics of this case were similar to those of medulloblastoma of the cerebellar vermis in humans. The authors were able to remove almost all of the tumour. The cat was discharged from hospital on day 22 after surgery, but died on day 45. The excised tissue was histologically diagnosed as medulloblastoma.     

Medulloblastoma in a cat: clinical and MRI findings

A two-year-old, castrated crossbred cat presented with loss of balance and anorexia. A mass of the caudal aspect of the cerebellum was revealed by magnetic resonance imaging (MRI). The mass was hypointense on T1 -weighted images, iso- and hyperintense on T2-weighted images and was enhanced by intravenous gadolinium contrast medium. The MRI characteristics of this case were similar to those of medulloblastoma of the cerebellar vermis in humans. The authors were able to remove almost all of the tumour. The cat was discharged from hospital on day 22 after surgery, but died on day 45. The excised tissue was histologically diagnosed as medulloblastoma.     

Dandy-Walker malformation in two calves

Two calves with unusual malformations of the skull and brain are described. Both calves showed doming of the posterior skull due to enlargement of the posterior fossa and cyst-like dilatation of the fourth ventricle. The cystic dilatation of the fourth ventricle formed a meningocoele in one calf. Aplasia of the cerebellar vermis was present in both calves. One calf showed agenesis of the corpus callosum. These features are consistent with the Dandy-Walker malformation of man.