Magnetic resonance imaging of neuronal ceroid lipofuscinosis in a border collie

A castrated male border collie 23 months of age weighing 19.4 kg was referred to the Animal Medical Center of Nihon University with complaints of visual disturbance and behavioral abnormality, hyperacusis and morbid fear. The MRI examination revealed the slight dilated cerebral sulci and cerebellar fissures and left ventricular enlargement. This is the first report of MRI findings of canine neuronal ceroid lipofuscinosis.     

Clinical and pathologic features of ceroid lipofuscinosis in two Australian cattle dogs

A lysosomal storage disease was diagnosed in 2 Australian Cattle Dog siblings, using light and electron microscopic evaluation. Both dogs developed clinical signs of disease at about 1 year of age. Vision and motor function deteriorated over several months; by 2 years of age, the dogs were blind and had progressive ataxia. Cytoplasmic inclusions with ultrastructural patterns characteristic of ceroid lipofuscin were observed in most neurons examined and in the cells of several other parenchymatous tissues. Biochemical studies, including determination of lysosomal enzyme activities, excluded several other lysosomal storage diseases. In these dogs, the clinical and pathologic features of the disease were similar to those of the juvenile subtype of ceroid lipofuscinosis (Batten disease) in human beings.     

Neuronal ceroid lipofuscinosis in Merino sheep

OBJECTIVE: To characterise neuronal ceroid lipofuscinosis (NCL) in Merino sheep. DESIGN: A prospective clinical, pathological, biochemical and genetic study. PROCEDURE: NCL cases were studied from a medium-wool Merino flock, the stud of origin of its replacement rams, and an experimental flock established at the University of Sydney. RESULTS: Behavioural changes and visual impairment were first detected at 7 to 12 months of age and progressed, with associated motor disturbances and at later stages seizures, to premature death by 27 months of age. At necropsy there was severe cerebrocortical atrophy associated with neuronal loss, astrocytosis and the presence in neurons of eosinophilic intracytoplasmic storage bodies with the characteristics of a lipopigment. In the retina there was progressive loss of photoreceptor cells. Storage bodies isolated from fresh brain, liver and pancreas formed electron-dense aggregates and coarse multilamellar and fine fingerprint profiles ultrastructurally, and consisted mainly of the hydrophobic protein, subunit c of mitochondrial ATP synthase. A homozygosity mapping approach localised the gene causing the disease in Merino sheep to the chromosomal region (OAR7q13-15) associated with NCL in South Hampshire sheep. CONCLUSION: NCL in Merino sheep is a subunit c-storing disease, clinically and pathologically similar to NCL in South Hampshire sheep. We propose that the disease in both breeds represents mutation at the same gene locus in chromosomal region OAR7q13-15.     

Extrahepatic biliary atresia in a border collie

Progressive lameness and leg pain were the predominant clinical signs in a 17-week-old male border collie presented for examination. On clinical investigation, extrahepatic cholestasis in association with rickets due to inadequate vitamin D resorption was diagnosed. The dog was treated parenterally with vitamin D and a cholecystoduodenostomy was performed. At 25 days postsurgery the lameness had resolved and bone structure was radiographically normal. However, at six weeks postsurgery, the dog's condition deteriorated rapidly and euthanasia was finally performed at eight weeks postsurgery. At postmortem examination, Toxocara canis nematodes were found to have invaded the biliary system via the anastomosis between the gallbladder and duodenum, causing biliary and hepatic toxocariasis. The cause of the primary extrahepatic cholestasis was atresia of the common bile duct at the hepatic end. The liver tissue showed microscopic lesions of chronic extrahepatic cholestasis as well as acute inflammation associated with the nematode invasion. There was no postmortem evidence of bone lesions. Extrahepatic biliary atresia is extremely rare in animals and has not been described before in dogs. In contrast, it represents the most common cause of congenital cholestasis in children, occurring in approximately one per 10,000 to 15,000 live births.     

Central tarsal bone fracture in the border collie

Fracture of the plantar process of the central tarsal bone together with a dorsomedial displacement of the body of the bone was seen in six border collies. All injuries occurred during free exercise, with no extrinsic trauma. Three dogs had concomitant tarsal fractures. Primary treatment was by lag screwing the central tarsal bone to the fourth tarsal bone. All cases eventually made an excellent recovery. The superficial radiographic appearance was of a luxation of the bone as reported in a previous series, but appraisal of the radiographs showed evidence of fracture in all cases. A cadaver study to assess the mechanism of luxation showed that it is unlikely to occur naturally.     

A variant form of neuronal ceroid lipofuscinosis in American bulldogs

Neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative diseases characterized by accumulations of autofluorescent lipopigments within cells of the nervous system. Nine related American Bulldogs demonstrated dysmetria in all limbs and paraparesis. Nonambulatory tetraparesis was observed only in the later stages of the disease. The clinical signs developed between 1 and 3 years of age and were slowly progressive over several years, which is inconsistent with most reports in other breeds. Results from blood tests for 8 different lysosomal storage diseases on 4 affected and 6 related but unaffected dogs were negative. Four affected dogs were euthanized and histopathologic examinations showed diffuse accumulations of periodic acid-Schiff-positive inclusions in neurons and axonal spheroids along the entire neuraxis and retinae. The most severe lesions were in the brainstem proprioceptive nuclei and spinal cord, consistent with clinical signs. The storage material was autofluorescent and immunohistochemically positive for products of lipid peroxidation. Ultrastructural analysis was consistent with NCL. Pedigree analysis supports an autosomal-recessive mode of inheritance. NCL has not been previously reported in the American Bulldog and these findings suggest a variant form of the canine disease.     

Idiopathic Horner's syndrome in collie dogs

Seven cases of idiopathic Horner's Syndrome in the Collie are described. Five males and two females presented with unilateral miosis, ptosis of the upper eyelid, enophthalmos and protrusion of the third eyelid. Thorough examination, pharmacological testing with phenylephrine, complete blood counts and radiography of the tympanic bullae and thorax were performed. The etiology was not identified in any of the cases. Clinical signs improved with pharmacologic testing within 20–40 min. In five dogs, total resolution of clinical signs was observed at 4 and 16 weeks after their initial appearance. Pharmacological testing suggested that the deficit could be at the preganglionic neuron.     

Computed tomographic findings of ceroid lipofuscinosis in a dog.

A two-year and seven-month-old, castrated male border collie was presented for a two-month history of progressive neurological signs including blindness, ataxia, dementia, and partial seizures. A complete blood count, serum biochemical profile, urinalysis, thoracic radiographs, and cerebrospinal fluid analysis were within reference ranges. Computed tomography (CT) of the brain showed dilatation of the ventricles and atrophy of the cerebral cortex. A central nervous system (CNS) storage disease was suspected, and the dog was euthanized due to a poor prognosis. Light and electron microscopic examination revealed neuronal degeneration with pigment accumulation in neurons of the CNS, in ganglia of the peripheral nervous system, and in several non-nervous tissues. Ceroid lipofuscinosis was diagnosed based on the microscopic and ultrastructural lesions detected. This is the second report of CT findings in a canine clinical patient with ceroid lipofuscinosis.     

Neuronal ceroid lipofuscinosis: clinical and morphologic findings in nine affected Polish Owczarek Nizinny (PON) dogs

OBJECTIVE: The aim of this study was to characterize the clinical and morphologic features of neuronal ceroid lipofuscinosis (NCL) in the Polish Owczarek Nizinny (PON) breed of dog. ANIMALS: Nine Swedish PON dogs of both sexes were included in the study. PROCEDURE: All dogs underwent a detailed clinical evaluation, with emphasis on ophthalmic exams. Histopathology and electron microscopy were performed on the eyes, brain and various internal organs. Immunohistochemical staining for detection of sphingolipid activator proteins (SAPs) and mitochondrial ATP synthase (SCMAS) was performed on the eyes and brain. RESULTS: The dogs showed behavioral abnormalities, motor disturbances and visual impairment or blindness. Pupillary responses were abnormal while fundus changes varied from normal to severe retinal atrophy. Electroretinography (ERG) showed variable changes, from slight alterations in the process of dark adaptation to severely reduced or nonrecordable ERG a- and b-wave amplitudes. Histopathology revealed intracytoplasmic storage bodies within neurons of the brain and in retinal cells, especially the retinal pigment epithelium (RPE). Round to oval granular type of inclusion bodies, known as granular osmiophilic dense deposits (GRODS), were found in neuronal cells in the brain and in the retina. Immunohistochemistry identified the storage material in the brain and retina as consisting of SAPs. CONCLUSION: The presently described NCL disease in PON dogs shows similarities to previously recorded cases in the Miniature Schnauzer. The closest human equivalent to this disease is infantile NCL (CLN1), in which the major stored proteins are SAPs and the ultrastructure of the inclusion bodies of neuronal cells is granular.     

Hypercholesterolaemia in a family of rough collie dogs

A family of five privately owned rough collie dogs was referred for corneal lipidosis and also suffered from hypercholesterolaemia. The hypercholesterolaemia was characterised by an increase in the alpha-2 high density lipoprotein-1 band and was due to an increase in the cholesterol content of the very low density lipoprotein, low density lipoprotein and possibly the high density lipoprotein-1 fractions. A low-fat and energy-restricted diet did not reduce either total cholesterol or the corneal lipidosis. Corneal lipidosis regressed with short-chain fructo-oligosaccharide supplementation. However, the effects of short-chain fructo-oligosaccharides on total cholesterol were transient and variable.     

The cutaneous histology of dermatomyositis in collie dogs

Cutaneous lesions of 36 collie dogs affected with dermatomyositis were reviewed. The most common histologic features were follicular atrophy and perifollicular inflammation in 30 dogs, which correlated with alopecia clinically. Other less common findings included formation of colloid bodies, basal cell vacuolation, and subepidermal vesiculation. Results indicated that the most diagnostic cutaneous histologic features of dermatomyositis may be follicular atrophy and inflammation.     

Suspected inherited cerebellar neuroaxonal dystrophy in collie sheep dogs

A cerebellar neuroaxonal dystrophy in working collie sheep dogs from two properties in New Zealand and one property in Australia is described. Clinical signs developed from 2–4 months of age and included hypermetria, wide-based stance, difficulty in maintaining balance, intention tremor and ataxia. Numerous spheroids, associated with mild Wallerian degeneration, were present in the central cerebellar, adjacent peduncular and folia white matter, and associated cerebellar roof and lateral vestibular nuclei. The history of several affected pups in litters from successive matings of the same sire and dam is suggestive of an autosomal recessive mode of inheritance.     

Assessment of plasma carnitine concentrations in relation to ceroid lipofuscinosis in Tibetan Terriers

OBJECTIVE: To determine whether the late onset form of inherited ceroid lipofuscinosis (CL) in Tibetan Terriers is accompanied by low plasma carnitine concentrations prior to the appearance of clinical signs. ANIMALS: 129 healthy Tibetan Terriers, 12 Tibetan Terriers with CL, and 95 healthy purebred dogs of other breeds. PROCEDURE: After withholding food, blood samples were collected from all dogs into tubes containing EDTA. Blood samples were analyzed for plasma-free carnitine and acyl-carnitines concentrations. RESULTS: Neither the mean plasma total carnitine concentration nor the mean fraction of carnitine in the free form differed significantly between Tibetan Terriers with CL and healthy Tibetan Terriers. Among Tibetan Terriers and the general dog population, plasma carnitine concentration increased with age. Castrated males had an overall increase in plasma carnitine concentrations and variability, compared with sexually intact males. By comparison, plasma carnitine concentrations were not significantly different between spayed and sexually intact females. The mean plasma carnitine concentration in the Tibetan Terriers was approximately 22% higher than in the general population of healthy dogs of other breeds. CONCLUSIONS AND CLINICAL RELEVANCE: Contrary to what is seen in early onset CL in English Setters and in humans with some forms of CL, plasma carnitine concentrations are not decreased in the late-onset disorder in Tibetan Terriers. Our large-scale study establishes reference range values for plasma carnitine concentrations in dogs as functions of age and sex that will be useful in evaluating potential carnitine deficiencies in other disorders in dogs.     

Neuronal ceroid lipofuscinosis in a Vietnamese pot-bellied pig (Sus scrofa)

The neuronal ceroid ipofuscinoses (NCL) are a group of heritable, neurodegenerative, storage diseases, typically with an autosomal recessive mode of inheritance. Cytoplasmic accumulation of storage material in cells of the nervous system and, variably in other tissues, characterizes NCL. NCL has been reported in many animal species, but to the authors' knowledge, this is the first report of the disease in a pig. Blindness and seizures are common clinical signs of disease, neither of which was a feature in this pig. The lesions were restricted to the central nervous system, which was diffusely affected, with the most severe lesions in the hippocampus, cerebral cortex, and cerebellum. The histologic lesions included neuronal loss and gliosis, which contributed to mild cerebrocortical and cerebellar atrophy and accumulation of autofluorescent storage material in neurons and glial cells. The storage material had morphologic, histologic, and ultrastructural properties typical of NCL.     

Binding characteristics of ivermectin in plasma from collie dogs

Two types of experiments were performed in an effort to demonstrate a role for plasma proteins in determining the amount of ivermectin available for transport across the blood-brain barrier of collie dogs sensitive to the effects of the compound. The solubility of ivermectin in plasma from non-sensitive and sensitive collies was measured and found to be identical at 100 g/ml. An assay for measuring the low affinity binding interaction of ivermectin with plasma components was developed. The amount of ivermectin bound per unit of plasma was the same for samples from sensitive and non-sensitive dogs. Dog serum albumin and the high density lipoprotein portion of the plasma were both capable of binding ivermectin. No differences in the binding characteristics of ivermectin in plasma from ivermectin sensitive and non-sensitive collies were found.     

Suspected inherited cerebellar neuroaxonal dystrophy in collie sheep dogs

A cerebellar neuroaxonal dystrophy in working collie sheep dogs from two properties in New Zealand and one property in Australia is described. Clinical signs developed from 2-4 months of age and included hypermetria, wide-based stance, difficulty in maintaining balance, intention tremor and ataxia. Numerous spheroids, associated with mild Wallerian degeneration, were present in the central cerebellar, adjacent peduncular and folia white matter, and associated cerebellar roof and lateral vestibular nuclei. The history of several affected pups in litters from successive matings of the same sire and dam is suggestive of an autosomal recessive mode of inheritance.     

Coxofemoral luxation in a border collie as a complication of a Clostridium tetani infection

A four-month-old male, entire, border collie was presented to the Queen Mother Hospital for Animals with a two day history of muscular spasms and "Risus sardonicus". Tetanus was diagnosed, and the dog was treated with tetanus antitoxin, antibiotics and supportive therapy. Coxofemoral luxation resulted as a complication of the tetanus and was successfully managed by performing a femoral head and neck excision. This is the first report of joint luxation associated with Clostridium tetani infection in a dog.