Sacral osteochondrosis dissecans in a Bernese Mountain Dog: diagnosis and treatment

A 18-month-old female Bernese Mountain Dog with chronic pain at jumping, extension of the right hind leg and paresis of the tail was referred to the Neurological Service of the Veterinary Hospital of the University of Zurich. Upon radiological examination a mineralised fragment at the dorsal aspect of the endplate of S1 was detected. The diagnosis of Osteochondrosis dissecans was confirmed by linear and computed tomography as well as histologic examination of the fragment, which was surgically removed. Preoperative imaging allowed a minimal surgical approach using a unilateral, modified dorsal laminectomy. Outcome was evaluated by neurological reevaluation and a CT scan performed 6 months after surgery.     

Early retinopathy in the Bernese Mountain Dog in France: preliminary observations

The objective of the study was to describe a form of early retinopathy in the Bernese Mountain Dog in France. Sixty-two Bernese Mountain Dogs (38 males and 24 females), whose ages ranged from 2 months to 9 years, were examined over a period of 3 years. Visual behavior, pupillary light reflexes, menace responses and ocular fundi were evaluated in all animals. Electroretinography (ERG) was performed on six of the affected dogs after dark adaptation. Fluorescein angiography (FA) was performed on one affected dog. Whenever possible, the pedigrees of the affected dogs were evaluated. A histological examination of the retina was performed on one of the affected dogs. Eight dogs (seven males and one female) were diagnosed with retinopathy with an early onset of clinical signs. (Four dogs were aged between 3 months and 1 year, two dogs were aged 2 and 3.5 years, and one dog was 7 years old.) Night vision was impaired in most of the dogs. Retinopathy was characterized ophthalmoscopically by a bilateral, symmetrical horizontal zone of tapetal hyper-reflectivity adjacent to and above the optic disc, and sometimes by peri-papillary hyper-reflectivity. ERG changes included a reduction in b-wave amplitude varying from one case to another. Fluoroscein angiography demonstrated an ischemic-type alteration with epitheliopathy opposite the hyper-reflective zone. Pedigree examinations suggested a familial predisposition. The histological examination indicated photoreceptor degeneration that was more pronounced in the central tapetal zone. In France, retinopathy in the Bernese Mountain Dog involves an early retinal degeneration that produces specific manifestations of the ocular fundus, night visual impairment or blindness, and has familial transmission.     

Degenerative myelopathy in a cat

Degenerative myelopathy was diagnosed in a 6-year-old cat that had progressive ataxia, posterior paresis, and loss of conscious proprioception over a period of 8 months. Corticosteroid therapy did not alleviate clinical signs, and the cat was euthanatized. Microscopic examination of the spinal cord revealed diffuse degeneration of myelin attended by marked astrocytosis. The degenerative changes were most marked in the thoracolumbar segment. The cause of the degenerative lesions was not apparent.     

Degenerative myelopathy in a German shepherd

A 9-year-old male German Shepherd had marked stumbling, staggering and weakness in both rear limbs. Pelvic radiographs revealed only mild hip dysplasia, while survey spinal radiographs and a myelogram revealed only areas of possible pachymeningitis. Results of CSF analysis were normal. Degenerative myelopathy was suspected, but a mitogen response assay failed to confirm this diagnosis. Another mitogen response assay, performed several months later, again failed to indicate degenerative myelopathy as the cause of clinical signs. The dog's condition worsened and the animal was euthanized. At necropsy, classic histopathologic lesions of degenerative myelopathy were noted in the thoracic spinal cord.     

Degenerative myelopathy associated with cobalamin deficiency in a cat

A severe myelopathy was observed in a 9-year-old neutered male cat with a clinical history of chronic pancreatitis associated with deficiency of serum cobalamin and folates concentrations, and progressive spinal ataxia. The spinal cord lesions mainly involved the dorsal columns of the caudal cervical and cervico-thoracic segments, and were characterized by diffuse vacuolated myelin sheaths and axonal degeneration, marked gliosis, fibrosis and presence of gitter cells. The pancreas showed severe atrophy of the exocrine tissue, periductular fibrosis and infiltration of inflammatory cells, consistent with chronic interstitial pancreatitis. This condition can be accountable for cobalamin deficiency, as the pancreas is the only source of intrinsic factor in cats. The spinal cord lesions in the cat of this report resembled the subacute combined degeneration of the spinal cord described in human beings with cobalamin deficiency and hence a similar pathogenetic mechanism is hypothesized.     

Malignant histiocytosis in Bernese Mountain dogs

Malignant histiocytosis was diagnosed in 10 male and 1 female Bernese Mountain Dogs. Nine of these dogs were closely related. The disease was characterized by a rapidly progressive and inevitably fatal course. Clinical signs varied, but lethargy, anorexia, weight loss, and respiratory and CNS abnormalities predominated. The lungs were the primary site of tumor involvement in 10 dogs. The eleventh dog had lymphadenopathy and severe anemia. Metastatic lesions were detected in all dogs. Anaplastic pulmonary carcinoma was diagnosed originally in 6 of the 11 cases, but this diagnosis was changed to malignant histiocytosis after electron microscopic examination of tissues and immunohistochemical identification of histiocytic markers in the tumor cells.     

Degenerative myelopathy in two equids

Degenerative myelopathy was diagnosed in a donkey Equus asinus and a Welsh pony Equus caballus. Both equids were presented for gradually progressive incoordination. Neurologic examination revealed symmetrical weakness and ataxia which was much more prominent in the rear limbs than in the front limbs. Laboratory tests including a complete blood count, serum biochemistry, cerebrospinal fluid analysis and lateral cervical radiographs were performed in both equids and were unremarkable. Both equids were euthanized and microscopic examination of the spinal cords revealed diffuse neuronal degeneration, demyelination and neuraxonal dystrophy.     

Genetic variation and genetic trends in hip and elbow dysplasia in Swedish Rottweiler and Bernese Mountain Dog

The aim of this study was to estimate genetic parameters and genetic trends for hip (HD) and elbow dysplasia (ED) in Swedish Rottweiler (RW) and Bernese Mountain Dog (BMD). Analyses were based on screening results of hip status for 14 693 RW and 8221 BMD and elbow status for 11 891 RW and 7963 BMD, as well as pedigree data for 16 614 RW and 9835 BMD, recorded by the Swedish Kennel Club. Components of (co)variance and breeding values were obtained with a mixed linear animal model. The model included the fixed effects of sex, birth month, age at screening and a combined random effect of clinic and year of examination. The need to include genetic groups for phantom parents in the model was evaluated by comparison of two different models: with and without genetic groups. Estimated heritabilities for HD and ED were between 0.34 and 0.42. The genetic correlation between the traits was weak and positive for RW (r_g = 0.23 ± 0.05) and not different from zero for BMD (r_g = 0.06 ± 0.06). F‐statistics of the genetic group effects were not significant, implying that genetic groups do not need to be included in the model. Genetic trends indicated a genetic improvement in both traits. However, a faster genetic progress is expected if selection is based on predicted breeding values rather than phenotype. Based on the results, a statistical model for routine prediction of breeding values for HD and ED in Swedish dogs was suggested.     

Disseminated histiocytic sarcoma with peripheral blood involvement in a Bernese Mountain dog

Abstract: A 6‐year‐old Bernese Mountain dog was presented with a history of lethargy and weight loss of 2 weeks duration. On physical examination the dog had pale mucous membranes and tachypnea. Ultrasound examination revealed hepatomegaly, splenomegaly, and mesenteric lymphadenomegaly. Results of a CBC included marked normocytic normochromic nonregenerative anemia, marked thrombocytopenia, and moderate leukocytosis with mild neutrophilia and a large population of unclassified round cells (6.2 × 10³/μL). The unclassified cells occasionally were bi‐ or multinucleated and had variably abundant pale basophilic cytoplasm that contained multiple irregular clear vacuoles and occasionally erythrocytes. Fine needle aspirate specimens of the mesenteric lymph nodes and spleen were composed of a population of round pleomorphic cells with the same features as the circulating cells. On flow cytometric analysis of peripheral blood, the unclassified cells expressed CD18, CD45, CD11c, CD1c, and CD14; immunocytochemical analysis of blood smears also indicated the cells were positive for CD1c, CD1a, and CD11c. The dog died a few hours after referral. The histologic interpretation of samples collected from spleen, liver, and lymph nodes was malignant neoplasia of histiocytic origin. Immunohistochemical staining yielded negative results for CD11d, a marker of red‐pulp macrophages, ruling out hemophagocytic histiocytic sarcoma. Based on clinical and pathologic findings, the final diagnosis was disseminated histiocytic sarcoma (DHS) with peripheral blood involvement. To our knowledge, DHS in a dog with evidence and immunophenotyping of neoplastic cells in peripheral blood has been reported only rarely.     

Degenerative myelopathy in a family of Siberian Husky dogs

Three closely related, Siberian Husky dogs had chronic progressive paresis and ataxia with muscle atrophy in the hindlimbs. Radiologic and myelographic examination of the spine revealed no abnormalities. On histologic examination, disseminated degeneration of the white matter, particularly in the thoracic segments, was seen. The clinical and pathological findings were similar to those described in aging large dogs with so-called degenerative myelopathy. The cause of this disease is unknown but the fact that these 3 Huskies were closely related suggest that hereditary factors may play a role.     

Complement C3 in Bernese Mountain dogs

Background: Previous research suggests that low serum concentrations of the third component of complement (C3) are associated with both the susceptibility to infectious agents such as Borrelia burgdorferi and the development of glomerular disease. We hypothesized that low levels of C3 are associated with the coincident occurrence of B. burgdorferi infection and glomerulonephritis in Bernese Mountain dogs. Objectives: The aims of this study were to evaluate the serum concentration of C3 in Bernese Mountain dogs with and without antibodies against B. burgdorferi and to compare this concentration with that of healthy control dogs. Methods: Eighty‐three clinically healthy Bernese Mountain dogs and 46 control dogs were included. Antibodies against B. burgdorferi were determined using an ELISA with a whole cell sonicate as antigen. Results were confirmed using Western blot. C3 was measured using a single radial immunodiffusion test. Results were reported as the percentage concentration of C3 compared with that in pooled preserved canine serum (100% C3 concentration). Results: Median C3 concentration was 128.5% in Bernese Mountain dogs with antibodies against B. burgdorferi, 133.5% in B. burgdorferi‐negative Bernese Mountain dogs, 87.8% in positive control dogs, and 102.2% in negative control dogs. Within Bernese Mountain and control groups, C3 was lower in dogs with antibodies against B. burgdorferi compared with those without. Percentage concentration of C3 was higher in healthy Bernese Mountain dogs compared with control dogs. Conclusion: Low C3 concentration is not an explanation for the high prevalence of B. burgdorferi infections and glomerular disease in Bernese Mountain dogs.     

Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy

Background

Previous reports associated 2 mutant SOD1 alleles (SOD1:c.118A and SOD1:c.52T) with degenerative myelopathy in 6 canine breeds. The distribution of these alleles in other breeds has not been reported.

Objective

To describe the distribution of SOD1:c.118A and SOD1:c.52T in 222 breeds.

Animals

DNA from 33,747 dogs was genotyped at SOD1:c.118,SOD1:c.52, or both. Spinal cord sections from 249 of these dogs were examined.

Methods

Retrospective analysis of 35,359 previously determined genotypes at SOD1:c.118G>A or SOD1:c.52A>T and prospective survey to update the clinical status of a subset of dogs from which samples were obtained with a relatively low ascertainment bias.

Results

The SOD1:c.118A allele was found in cross‐bred dogs and in 124 different canine breeds whereas the SOD1:c.52T allele was only found in Bernese Mountain Dogs. Most of the dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A homozygotes, but 8 dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A/G heterozygotes and had no other sequence variants in their SOD1 amino acid coding regions. The updated clinical conditions of dogs from which samples were obtained with a relatively low ascertainment bias suggest that SOD1:c.118A homozygotes are at a much higher risk of developing degenerative myelopathy than are SOD1:c.118A/G heterozygotes.

Conclusions and Clinical Importance

We conclude that the SOD1:c.118A allele is widespread and common among privately owned dogs whereas the SOD1:c.52T allele is rare and appears to be limited to Bernese Mountain Dogs. We also conclude that breeding to avoid the production of SOD1:c.118A homozygotes is a rational strategy.     

Degenerative myelopathy in an adult miniature poodle

Degenerative myelopathy was diagnosed at necropsy of an adult Miniature Poodle with a 33-month history of progressive pelvic limb ataxia and proprioceptive deficit. Microscopic examination of the cord revealed diffuse degenerative myelopathy. Degenerative myelopathy is usually seen in adult, large-breed dogs and progresses over a period of months. In this case, the myelopathy progressed slowly and the degree of paralysis became more extensive than usually seen.     

Gain‐of‐function mutation in PTPN11 in histiocytic sarcomas of Bernese Mountain Dogs

Histiocytic sarcoma (HS) is an aggressive malignant neoplasm of dendritic cell origin that is common in certain breeds of dogs. High prevalence of fatal, disseminated HS has been described in Bernese Mountain Dogs (BMDs). Support for genetic predisposition to develop HS has been presented in several studies, but to date, causative genetic events have not been reported. In addition, no driver mutations have been identified in tumours. Recently, E76K gain‐of‐function mutation in SHP2 encoded by the PTPN11 gene has been described in human histiocytic malignancies. In our study, we identified the PTPN11^E76K in HS of BMDs. Amplification of exon 3 of the PTPN11 gene followed by Sanger sequencing was used to detect the mutation and estimate the prevalence in HS from 30 BMDs, 13 Golden Retrievers and 10 other dog breeds. The overall prevalence of PTPN11^E76K in HS of BMDs was 36.67% compared with 8.69% in other breeds. No mutation was identified in normal tissues from 10 BMDs with HS that carried the mutation and 12 control dogs with no neoplastic disease, including 6 BMDs. Increased immunoreactivity for AKT, phosphorylated ERK1/2 and phosphorylated AKT in a small subset of BMDs with PTPN11^E76K suggests that a gain‐of‐function might be mediated by the ERK and AKT pathways. These data suggest PTPN11^E76K as an important driver mutation of HS in BMDs. This information may not only aid in unravelling the tumourigenic events associated with HS in BMDs, but also help in identifying more promising therapeutic strategies.     

The presence of antiphospholipid antibodies in healthy Bernese Mountain Dogs

Background

The role of antiphospholipid antibodies in the prolonged activated partial thromboplastin time (aPTT) previously identified in healthy Bernese Mountain Dogs remains unknown. In people, an isolated prolonged aPTT without evidence of bleeding might be because of a thrombophilic condition caused by antiphospholipid antibodies.

Objective

To examine if prolonged aPTT in healthy Bernese Mountain Dogs is because of antiphospholipid antibodies.

Animals

Twenty‐two healthy Bernese Mountain Dogs and 10 healthy adult dogs of various breeds.

Methods

Prospective case control study. Healthy Bernese Moutain Dogs were examined twice over 6 months. Dogs were investigated for the presence of lupus anticoagulants and anticardiolipin (aCL) antibodies by the use of multiple aPTT tests with low and high lupus anticoagulant sensitivities, a mixing study, and an ELISA test for aCL antibody optical density to detect solid phase antiphospholipid antibodies.

Results

In all, 15 of 22 healthy Bernese Mountain Dogs were positive for lupus anticoagulants. The Bernese Mountain Dogs had markedly higher levels of aCL antibodies compared with the control dogs (P = .006). In all, 7 of 21 of the Bernese Mountain Dogs were positive for both lupus anticoagulants and aCL antibodies, whereas 4 of 21 Bernese Mountain Dogs were negative for both.

Conclusions and Clinical Importance

Lupus anticoagulants and aCL antibodies could be the cause of prolonged aPTT in healthy Bernese Mountain Dogs. The importance of the antiphospholipid antibodies in the dogs remains unknown.