Spongy Degeneration with Cerebellar Ataxia in Malinois Puppies: A Hereditary Autosomal Recessive Disorder?

Background: There is a high incidence of hereditary degenerative diseases of the central nervous system in purebred dogs. Hypothesis: Cerebellar ataxia in Malinois puppies, caused by degenerative changes that predominate in cerebellar nuclei and the granular cell layer, is a hereditary disorder that is distinct from cerebellar cortical abiotrophies. Animals: Thirteen Malinois puppies with cerebellar ataxia. Methods: Retrospective study. Records of Malinois puppies with spongy degeneration of the cerebellar nuclei were analyzed including clinical signs, histopathological changes, and pedigree data. Results: Signs of cerebellar dysfunction were observed in puppies of both sexes from 5 different litters (1995–2009) of phenotypically normal parents. Clinical signs started before the age of 2 months and resulted in euthanasia of all puppies by the age of 13 weeks. Histopathology disclosed marked bilateral spongy degeneration of the cerebellar nuclei and vacuoles in the granular cell layer and foliate white matter of the cerebellum. In some puppies, discrete vacuoles in gray and white matter were present in other parts of the brain. Furthermore, spheroids and dilated myelin sheaths were observed. Pedigree data and segregation frequency support an autosomal recessive hereditary disorder. Conclusions and Clinical Importance: Malinois suffer from a hereditary spongiform degeneration that predominates in the cerebellum and causes an early onset of clinical signs with unfavorable prognosis. Future efforts should increase awareness among veterinarians and breeders and aim to identify underlying metabolic mechanisms and the affected genes.     

Periventricular and subcortical leukoencephalopathy in two dachshund puppies

Two wirehaired dachshund puppies were presented with generalized tremor and gait abnormalities characterized by mild ataxia, tetraparesis and slightly abnormal proprioception. Neurological examination led to the suspicion of a diffuse generalized white matter lesion. Computerized tomography and pathological examination revealed a remarkable unilateral dilatation of the lateral ventricles in each dog. Histopathological examination showed a severe reduction of stainable myelin, widespread mild perineuronal oedema with vacuolations and multifocal reactive astrocytosis affecting the subcortical and deep periventricular white, and to a lesser degree, grey matter of the cerebral hemispheres, most prominently at the level of the optic chiasm. Axons showed a moderately reduced packing density; some axons were irregularly shaped and slightly thickened. There was no evidence of myelin breakdown products and neurones appeared to be well preserved. Brain stem, cerebellum and spinal cord were normal, as was the peripheral nervous system. This leukoencephalopathy in two dachshund puppies most closely resembles human periventricular leukomalacia caused by pre- or perinatal hypoxia-ischaemia.     

Dilated cardiomyopathy in juvenile Portuguese Water Dogs

Dilated cardiomyopathy recently has been recognized in juvenile Portuguese Water Dogs. The purpose of this study was to evaluate unaffected and affected puppies by physical examination, electrocardiogram (ECG), echocardiogram, specific biochemical assays, and ultrastructure to document disease progression and to develop a method of early detection. Results of segregation analysis were consistent with autosomal recessive inheritance. Of 124 puppies evaluated clinically and echocardiographically, 10 were affected. No significant differences were found between unaffected and affected puppies for blood and myocardial carnitine or taurine concentrations, serum chemical variables, results of ophthalmological examinations, ECGs, or measurement of urine metabolites. Ultrastructural examination of myocardium from affected dogs revealed myofibrillar atrophy and small regions of myofibrillar degeneration, most prominently at the region of the intercalated discs. Only echocardiography allowed detection of affected puppies before clinical signs became evident. Echocardiography revealed a significant difference in the shortening fraction, E point to septal separation, and the end systolic and diastolic left ventricular internal diameters. Affected puppies were detected 1-4 weeks before the development of acute congestive heart failure.     

Hexachlorophene and cuprizone induce the spongy change of the developing rat brain by different mechanisms: the role of 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)

The goal of this research was to identify mechanisms responsible for the spongy change induced in rats after repeated hexachlorophene (HCP) or cuprizone (CPZ) dosing. Rats were dosed with 35 mg/kg HCP for 5 days followed by drug withdrawal for 7 days suffered spongy changes to the white matter of the cerebrum, cerebellum, medulla oblongata, and spinal cord that were accompanied by degeneration of oligodendroglia. The severity of both lesions increased prominently on day 5; however, the spongy change decreased and degeneration of oligodendroglia reversed on day 12 (7 days after dosing ceased). On day 12, cerebral cortex oligodendroglia were stained strongly by anti-CNPase. Other rats were fed for 8 days with powdered chow containing 1% (w/w) CPZ, which was then withdrawn for 16 days. The rats exhibited the spongy change in the white matter of the cerebrum and cerebellum as well as oligodendroglial cell death from day 3. The severity of both lesions increased prominently on day 8. Cerebral cortex oligodendroglia were stained strongly by anti-CNPase on days 3 to 8 and decreased to the control levels by day 24 (16 days after dosing ceased). Electron microscopy revealed that oligodendroglia frequently displayed apoptotic morphology. These findings suggest that CNPase expression was induced in the course of restoration following HCP-induced insults to oligodendroglia and the myelin sheath, and in the course of demyelination by CPZ-induced damage to oligodendroglia. However, the role of CNPase on both courses is unclear.     

Parvovirus infection in a Beagle colony

The clinical and pathological features of an outbreak of parvovirus infection are described. In young puppies these were vomiting, diarrhoea and myocarditis whereas in older animals they were weight loss and enteropathy. Other features seen were interstitial pneumonia, lymphoid depletion and, in one dog, renal tubular degeneration. The haematological picture was inconsistent, a reduced number of circulating neutrophils or lymphocytes occurring in some cases whereas in others neutrophilia or lymphocytosis was present.     

Leucoencephalomalacia and Cerebral White Matter Vacuolar Degeneration in Two Related Labrador Retriever Puppies

Two Labrador Retriever dogs from a common dam had similar neurological deficits consisting of cortical blindness, dullness, and loss of previously learned habits. Both were examined at 5 months of age, and histopathological examination revealed leucoencephalomalacia and vacuolar degeneration of the cerebral white matter. Histopathologic findings in these 2 dogs differed from those reported previously in Labrador Retrievers with spongy degeneration of central nervous system white matter. A nonlittermate full sibling to 1 of these dogs was examined at 1.5 years of age for similar clinical signs that did not progress for the next 25 months.     

Progressive encephalomyelopathy and cerebellar degeneration in 10 captive-bred cheetahs

Progressive ataxia, with head tremor, developed in 10 captive-born cheetah cubs under six months of age. The condition was usually preceded by coryza and an ocular discharge. Initially the ataxia and weakness affected the hindquarters, then the forelegs, and head tremor developed later. Significant pathological changes were confined to the central nervous system. There was widespread Wallerian degeneration in the funiculi of the spinal cord (except those in the dorsal columns), in the medulla and in the cerebellum. In the cerebellum there was degeneration of Purkinje cells and of the molecular and granular cell layers. There was chromatolysis in the Purkinje cells, the ventral horn cells of the spinal cord and in the neurons of the lateral vestibular nucleus. The olivary nucleus was necrotic. There were foci of inflammatory cells in the molecular layer of the cerebellum and in the medulla. The cause of the disease remains unknown.     

Influence of inbreeding on litter size and the proportion of stillborn puppies in dachshunds

In the present study, factors influencing the litter size of puppies and the number and the proportion of stillborn puppies per litter were analysed in normally sized German dachshounds. Data was available for litters registered from 1987 to 2002 in the German dachshound kennel club. The records studied here contained 42,855 litters. The mean litter size was 5.22 +/- 2.01 puppies. The proportion of puppies born dead per litter was 6.6%. The age of dam, the puppy's year and month of birth, the hair type and the inbreeding coefficients of the puppies, the sire and the dam were significant on the litter size and the number and the proportion of puppies born dead. The litter size decreased and the percentage of puppies born dead increased with increasing inbreeding coefficients of the puppies, dams and sires. The increase of the inbreeding coefficient of the puppies by 1% led to a 0.06% higher percentage of puppies born dead per litter. The increase of the inbreeding coefficients of the dam and the sire by 1% resulted in 0.02% and 0.007% higher percentages of puppies born dead. Young and older dams had smaller litter size than middle-aged dams. The percentage of puppies born dead per litter increased with an increasing age of the dam. In the recent birth years, the litter size and the percentage of puppies born dead increased in German dachshounds.     

Mass screening of Irish wolfhound puppies for portosystemic shunts by the dynamic bile acid test.

Five hundred and sixty-six Irish wolfhound puppies aged six to 15 weeks were tested for congenital portosystemic shunts by the dynamic bile acid method. Plasma ammonia concentration was also measured in 165 of the puppies both fasting and postprandially. Nineteen puppies (3.4 per cent), nine males and 10 females, had portosystemic shunts. Smaller litters appeared to be more likely to contain affected puppies. The postprandial bile acid concentration was a reliable predictor of the presence of a shunt, with the highest concentration in a normal puppy being 38 mumol/litre and the lowest in an affected puppy being 43 mumol/litre. In contrast, fasting bile acid concentrations were normal in the majority of the affected puppies. There was considerable overlap in fasting plasma ammonia concentrations between normal and affected puppies (26 puppies, 15.8 per cent of those tested). Postprandial ammonia concentration appeared to give better separation between the two groups, apart from two individuals which produced bizarre results. It was concluded that the postprandial or dynamic bile acid test is an appropriate test for the mass screening of Irish wolfhound puppies for portosystemic shunts, and guidelines are proposed for the interpretation and follow-up of the test.     

Brodifacoum toxicosis in two neonatal puppies

Eight out of a litter of 13 puppies were either born dead or died within 48 hours of birth. Three puppies that died shortly after birth were necropsied. Two puppies had hemorrhage in the thoracic and peritoneal cavities, intestinal serosa, and meninges. The third puppy was smaller than the other two puppies but did not have detectable hemorrhage. Brodifacoum, a second-generation coumarin anticoagulant, was detected in livers from the two puppies with hemorrhage. The dam did not have clinical signs of coagulopathy before or subsequent to whelping. The owners were confident that the dog had not been exposed to rodenticide for at least 4 weeks before whelping. A presumptive diagnosis of in utero brodifacoum toxicity was made. To the authors' knowledge this is the first time a second-generation coumarin anticoagulant has been detected in the liver of a newborn animal. This case is also unique because the dam was unaffected, suggesting that fetuses are more susceptible to brodifacoum toxicity than adult animals.     

Maternal antibody, vaccination and reproductive failure in dogs with parvovirus infection

Summary. The maternal antibody (MAb) titre to canine parvovirus (CPV) was determined on consecutive serums from 39 puppies in 7 litters. Vaccination with inactivated CPV was performed at a variety of ages and the response of the puppies determined. Transfer of MAb was demonstrated in 71% (5/7) of the litters and persisted for up to 10 weeks in some litters. MAb titres of >20 precluded a vaccination response by puppies. Sixty- one per cent (8/13) of puppies responded to vaccination when the MAb titre was <20. However, no anamestic response occurred and in some cases a decrease in antibody titre was observed following a second vaccination. During an outbreak of canine parvovirus enteritis (CPE) in the kennel, 33 puppies developed clinical signs of enteritis. Of these puppies 85% (28) had MAb titres of <80 at the onset of clinical signs. Fifty per cent (4/8) of the puppies which responded to vaccination developed CPE, whereas 100% (5/5) of those that did not respond to vaccination developed CPE.
The results indicate that MAb may persist for up to 10 weeks and puppies with MAb in the titre range >20 to <80 do not respond to vaccination but are still susceptible to infection. It is also apparent that a significant minority of puppies with MAb <20 do not respond to vaccination.
An examination of the breeding records of the kennel for the 7 year period 1973–1981 demonstrated a sudden decrease in reproductive efficiency during and subsequent to 1978. This coincided with the recognition of cases of CPV infection in the kennel. It is suggested that further investigation is required into the possible role of CPV in reproductive failure.
The authors would like to thank H. Findlay, P. Hinchliffe, G. Griffiths and S. MacPhail for technical assistance and Dr G. Wilcox and R. Flower for helpful discussion and advice.     

An encephalomyelopathy in related Birman kittens

The clinical and morphological features of an encephalomyelopathy in five related Birman kittens are described. The five kittens showed hind limb paresis and ataxia which progressed to hind limb paralysis. Four of the kittens had bilateral nuclear cataracts. Histological examination revealed diffuse lesions within the brain and spinal cord, especially within the thoracolumbar spinal cord. The major changes were foci of spongy change and vacuolation along with Wallerian degeneration. All kittens were inbred and an inherited aetiology was suspected.     

Multifocal retinopathy of Great Pyrenees dogs

Forty-four related Great Pyrenees dogs were examined ophthalmoscopically. Focal retinal elevations, multiple gray-tan-pink subretinal patches, and discrete areas of tapetal hyper-reflectivity were seen in 19 dogs, ranging from 13 weeks to 10 years of age. These lesions varied in size from focal spots that were barely visible with the indirect ophthalmoscope to areas that were larger than the optic disc. Complete blood cell counts, serum biochemical profiles, urinalyses, and blood pressure measurements were completed on four affected dogs and all were within normal reference ranges. Photopic and scotopic electroretinography was completed and the a-wave and b-wave amplitudes and latencies were similar for affected and age-matched nonaffected Great Pyrenees and other normal dogs. Electroretinograms that were examined twice during a 3-year period on three affected adult dogs did not reveal significant progressive deterioration of the a or b-wave parameters. Fluorescein angiography was completed on four affected dogs of ages 1 (n = 2), 5, and 6 years. These angiograms were repeated in three of these dogs 1 year later. The blood ocular barrier was intact in these dogs but there was blocked choroidal fluorescence. Postmortem examination, light microscopy, scanning and transmission electron microscopy were performed on three affected puppies and two affected adult dogs. These examinations revealed that the lesions in the puppies were limited to bilateral multiple areas of retinal pigment epithelial vacuolation, hypertrophy, and apparent separation from Bruch's membrane, and multiple serous retinal detachments. The affected adult dogs had focal retinal degeneration and retinal pigment epithelial hypertrophy, hyperplasia and pigmentation. Pedigree analysis and test mating confirm that this condition is inherited, probably as an autosomal recessive trait. This condition develops at approximately 13 weeks of age and the focal areas of retinal detachment and retinal pigment epithelial vacuolation progress to permanent and stable focal areas of retinal degeneration, and retinal pigment epithelial hypertrophy and pigmentation.     

Dysautonomia in a family of German shorthaired pointers.

Four, 5-week-old German shorthaired pointers from a litter of five puppies were presented for evaluation of vomiting and diarrhea. The dam was euthanized for suspected dysautonomia, and the fifth puppy died 1 day prior to presentation. On presentation, two puppies had vomiting and diarrhea, and the other two appeared healthy. The results of testing supported the diagnosis of dysautonomia in the two affected puppies but not in the healthy puppies. On day 5 of hospitalization, one apparently healthy puppy developed vomiting and diarrhea and had supportive testing for dysautonomia. Dysautonomia was confirmed at necropsy in affected dogs.     

Seroconversion of puppies to canine parvovirus and canine distemper virus: a comparison of two combination vaccines

Sixty puppies were randomly assigned to receive one of two commercially available combination vaccines, and responses to the canine parvovirus and canine distemper virus components of the vaccines were determined by measuring serum antibody titers. The percentage of puppies that seroconverted to canine parvovirus was significantly higher and the mean time for seroconversion was significantly shorter for puppies that received one of the vaccines than for puppies that received the other vaccine. Percentages of puppies that seroconverted to canine distemper virus were not significantly different.     

Late onset of cerebellar abiotrophy in a Siamese cat

A late onset of cerebellar degeneration was diagnosed in a one-and-a-half-year-old Siamese cat. The animal had been presented with mild ataxia involving all four limbs. Over the following two years, the signs gradually progressed to severe incoordination, a frequent tendency to fall and a head tremor. The neurological signs were consistent with a diffuse cerebellar lesion and the cat was euthanased. Profound and diffuse Purkinje cell loss was found on histopathological examination, but no aetiological agent was detected.     

犬用配方羊奶粉对比格幼犬生长性能和肠道菌群的影响

为了探究配方羊奶粉对比格幼犬生长性能与肠道菌群的影响,选取12只15日龄比格犬,随机分为对照组和羊奶粉组,每组6只,对照组幼犬由母犬母乳喂养,羊奶粉组幼犬饲喂足量配方羊奶粉,每3d测量体重并计算体重增长,18 d后采集血样进行血常规、血清生化、免疫因子指标检测,采集粪样进行肠道菌群测序.结果 显示:相比于对照组,羊奶粉...     

Six-month prophylactic efficacy of moxidectin sustained release (SR) injectable for dogs against experimental heartworm infection in growing puppies

The purpose of this study was to assess the efficacy of moxidectin sustained release injectable for dogs (moxidectin SR, Fort Dodge Animal Health) in protecting growing puppies from experimental infection with the heartworm, Dirofilaria immitis, six months after treatment. The study involved 27 puppies, approximately 12 weeks of age at the beginning of the study, with nine puppies in each of three size classes. The small breed class included eight Pekingese and one purpose-bred small breed mongrel; the medium breed class included nine purpose-bred mongrels, and the large breed class included nine puppies with an anticipated adult weight >or=30-35 kg. Both genders were included with no attempt made to have equal numbers of male and female puppies. Puppies were blocked by weight within each size class and randomly assigned to three treatment groups of nine dogs. On Day 0, pups in two groups were injected subcutaneously with moxidectin SR, dosed to deliver 0.17 mg moxidectin/kg b.w. The third group was injected with sterile saline. Personnel making observations were blinded to the treatment status of the animals. Following treatment, puppies were observed for signs of adverse local and systemic reactions. Puppy weights and serum moxidectin levels were also monitored. On Day 180, puppies in all treatment groups were inoculated subcutaneously with 50 third-stage larvae of D. immitis. On Days 348 and 349, puppies were euthanatized and necropsied. Hearts and lungs were examined for adult heartworms. All animals in the saline control group were infected with an arithmetic mean of 39.22 adult heartworms each. Seventeen of 18 dogs in the moxidectin SR-treated groups were uninfected. One treated puppy was infected with a single adult heartworm. This infected individual was from the large breed size class and had the second highest percent increase in body weight. Based on arithmetic means, the heartworm recovery from all treated puppies represents a 99.86% reduction relative to the saline control. There were no adverse local or systemic reactions to treatment in any animal.     

Investigations into the prevention of prenatal and lactogenic Toxocara canis infections in puppies by application of moxidectin to the pregnant dog

Aim of the investigation was to examine whether two administrations of moxidectin to pregnant dogs could prevent pre-natal and lactogenic infections of puppies with reactivated Toxocara canis larvae. Four pregnant beagles, infected experimentally with 20 000 embryonated eggs of T. canis, were treated subcutaneously with 1 mg moxidectin per kg body weight on days 40 and 55 of pregnancy (5-13 days before parturition). One further dam and its puppies served as untreated control. Two applications of moxidectin completely prevented pre-natal and lactogenic infections in the puppies. Neither intestinal stages nor somatic larvae were found in the dams or their corresponding puppies. All puppies and dams of the treatment group remained coproscopically negative until 42 days after parturition. The administration of moxidectin did not show any side effects in the dams. None of the puppies of the treated dams showed any pathological abnormalities. In the untreated dam one adult and 26 somatic larvae of T. canis were detected at necropsy. All puppies of the untreated dam showed a patent T. canis infection from day 28 post-natum (p.n.); 296 pre-adult and adult stages of T. canis were spontaneously eliminated and 51 intestinal stages and five somatic larvae of T. canis were recovered at necropsy. In contrast to the puppies of the treated dams all negative control puppies showed blood eosinophilia after parturition and elevated liver enzyme levels.