A degenerative myelopathy in young German shepherd dogs

Two young male German shepherd dogs, six and seven months old, were evaluated for progressive hindlimb ataxia and paresis. Both dogs were found to be thin and poorly muscled on physical examination, and on neurological examination, the lesions were localised to the spinal cord between T2 and L4. Microscopical examination of the spinal cords demonstrated widespread axonal degeneration similar to that seen in aged German shepherd dogs with chronic degenerative radiculomyelopathy (CDRM), although the distribution of these changes was not identical to CDRM.     

Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs

BACKGROUND: Adult dogs with degenerative myelopathy (DM) have progressive ataxia and paresis of the pelvic limbs, leading to paraplegia and euthanasia. Although most commonly reported in German Shepherd dogs, high disease prevalence exists in other breeds. OBJECTIVE: Our aim was the clinical and histopathologic characterization of familial degenerative myelopathy (FDM) in Pembroke Welsh Corgi (PWC) dogs. ANIMALS: Twenty-one PWCs were prospectively studied from initial diagnosis until euthanasia. METHODS: Neurologic examination, blood tests, cerebrospinal fluid (CSF) analysis, electrodiagnostic testing, and spinal imaging were performed. Concentrations of 8-iso-prostaglandin F2alpha (8-isoprostane) were measured in CSF. Routine histochemistry was used for neuropathology. Deoxyribonucleic acid and pedigrees were collected from 110 dogs. RESULTS: Median duration of clinical signs before euthanasia was 19 months. Median age at euthanasia was 13 years. All dogs were nonambulatory paraparetic or paraplegic, and 15 dogs had thoracic limb weakness at euthanasia. Electrodiagnostic testing and spinal imaging were consistent with noncompressive myelopathy. No significant difference was detected in 8-isoprostane concentrations between normal and FDM-affected dogs. Axonal and myelin degeneration of the spinal cord was most severe in the dorsal portion of the lateral funiculus. Pedigree analysis suggested a familial disease. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical progression of FDM in PWC dogs was similar to that observed in other breeds but characterized by a longer duration. Spinal cord pathology predominates as noninflammatory axonal degeneration. Oxidative stress injury associated with 8-isoprostane production is not involved in the pathogenesis of FDM-affected PWC dogs. A familial disease is suspected.     

Daily controlled physiotherapy increases survival time in dogs with suspected degenerative myelopathy

The purposes of the study reported here were to evaluate the signalment and clinical presentation in 50 dogs with degenerative myelopathy, to evaluate whether mean survival time was significantly affected by various means of physiotherapy performed in 22 dogs, and to determine whether neurologic status, anatomic localization, or age at onset had an influence on survival time in dogs that received physiotherapy. We found a significant (P < .05) breed predisposition for the German Shepherd Dog, Kuvasz, Hovawart, and Bernese Mountain Dog. Mean age at diagnosis was 9.1 years, and both sexes were affected equally. The anatomic localization of the lesion was spinal cord segment T3-L3 in 56% (n = 28) and L3-S3 in 44% (n = 22) of the dogs. Animals that received intensive (n = 9) physiotherapy had longer (P < .05) survival time (mean 255 days), compared with that for animals with moderate (n = 6; mean 130 days) or no (n = 7; mean 55 days) physiotherapy. In addition, our results indicate that affected dogs which received physiotherapy remained ambulatory longer than did animals that did not receive physical treatment.     

Measurement of myelin basic protein in the cerebrospinal fluid of dogs with degenerative myelopathy

BACKGROUND: Analysis of cerebrospinal fluid (CSF) is part of a routine clinical workup in veterinary patients when neurologic disease is suspected. However, knowledge of particular protein markers of disease in CSF is limited. The concentration of myelin basic protein (MBP) in CSF is used as a biochemical marker in humans to evaluate demyelinating lesions in the central nervous system (CNS). OBJECTIVE: The purpose of this study was to evaluate an ELISA for determination of MBP concentration in the CSF of German shepherd dogs with degenerative myelopathy (GSDM). METHODS: Cross-reactivity of the anti-human polyclonal antibody used in a commercial ELISA (Active MBP ELISA, Diagnostic Systems Laboratories Inc, Webster, TX, USA) was tested with canine MBP by immunoblotting. CSF samples were collected from both the cisterna magna and the lumbar cistern of 8 clinically healthy control dogs and 8 German shepherd dogs clinically diagnosed with GSDM. MBP concentrations were measured in all CSF samples using the ELISA. RESULTS: The mean MBP concentration in CSF from the lumbar cistern of dogs with GSDM (3.13 -/+ 0.46 ng/mL) was significantly higher than that in the cisterna magna (0.70 -/+ 0.06 ng/mL) and from both cisternal (0.47 -/+ 0.07 ng/mL) and lumbar (0.94 -/+ 0.37 ng/mL) samples from control dogs. CONCLUSION: The MBP ELISA has potential as a supplemental test of CSF to diagnose demyelinating disorders in dogs.     

Immunohistochemical observation of canine degenerative myelopathy in two Pembroke Welsh Corgi dogs

Immunohistochemistry was performed to assess whether oxidative stress and/or denatured proteins play roles in the pathogenesis of canine degenerative myelopathy (DM). Two Pembroke Welsh Corgi (PWC) dogs with a homozygous mutation (c.118G>A) in the canine superoxide dismutase 1 (SOD1) gene were examined. The pathological features of the dogs were consistent with those of previous cases of DM in PWC. In the spinal lesions, diffuse SOD1 expression was observed in the neurons while no inclusion-like aggregates had formed, which disagreed with the findings of a previous study. A unique inducible nitric oxide synthase (iNOS) staining pattern in reactive astrocytes and a significant increase in ubiquitin immunoreactivity in the spinal lesions were also observed. These findings indicate the involvement of oxidative stress and the accumulation of ubiquitinated proteins in the pathogenesis of canine DM, whereas the role of SOD1 remains unclear.     

Molecular genetic and expression analysis of alpha-tocopherol transfer protein mRNA in German shepherd dogs with degenerative myelopathy

Degenerative Myelopathy (DM) is a progressive neurological disorder of the spinal cord preferentially occurring in German shepherd dogs. The pathogenesis of the disease is unknown. However, there are indications that vitamin E deficiency may be involved in the pathogenesis of DM. Therefore, we analyzed the expression and the nucleotide sequence of the canine alpha-tocopherol transfer protein (alpha Ttp) of German shepherd dogs with DM in order to determine whether a deficiency or a defect of the alpha Ttp could be a primary factor in the pathogenesis of DM, as found in human patients with Ataxia with vitamin E deficiency (AVED). The cDNA of the coding region of the canine alpha Ttp-mRNA was generated from total liver RNA using RT-PCR and 5' RACE technique. We determined the sequence of 707 out of 834 base pairs or 84.8% of the canine alpha Ttp coding region. Sequence comparison of canine alpha Ttp between affected and control dogs revealed no differences in either nucleotide or predicted amino acid sequence. Using Northern blot analysis alpha Ttp-mRNA expression was solely found in the liver of the dogs, rats and humans, while various other organs showed no alpha Ttp-mRNA expression. No significant differences in expression levels of canine alpha Ttp mRNA were found between DM and control dogs. Our data suggest that the canine alpha Ttp gene is unlikely to be involved in the pathogenesis of DM in German shepherd dogs.     

Evaluation of thyroid function in obese dogs and in dogs undergoing a weight loss protocol

Obesity and weight loss have been shown to alter thyroid hormone homeostasis in humans. In dogs, obesity is the most common nutritional problem encountered and weight loss is the cornerstone of its treatment. Therefore, it is important to clarify how obesity and weight loss can affect thyroid function test results in that species. The objectives of this study were to compare thyroid function in obese dogs and in lean dogs and to explore the effects of caloric restriction and weight loss on thyroid hormone serum concentrations in obese dogs. In the first experiment, 12 healthy lean beagles and 12 obese beagles were compared. Thyroid function was evaluated by measuring serum concentrations of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), thyrotropin (TSH), and reverse triiodothyronine (rT3) as well as a TSH stimulation test using 75 microg i.v. of recombinant human TSH. In the second experiment, eight obese beagles were fed an energy-restricted diet [average 63% maintenance energy requirement (MER)] until optimal weight was obtained. Blood samples for determination of TT4, FT4, TT3, TSH and rT3, were taken at the start and then weekly during weight loss. Only TT3 and TT4 serum concentrations were significantly higher in obese dogs as compared to lean dogs. In the second experiment, weight loss resulted in a significant decrease in TT3 and TSH serum concentrations. Thus obesity and energy restriction significantly alter thyroid homeostasis in dogs, but the observed changes are unlikely to affect interpretation of thyroid function test results in clinics.     

Treatment of dogs with lymphoma using a 12-week, maintenance-free combination chemotherapy protocol

BACKGROUND: Treatment of lymphoma in dogs by long-term chemotherapy has favorable results. However, the efficacy of short-term, maintenance-free treatment protocols on remission and survival times in dogs has not been determined. HYPOTHESIS: That treatment using a 12-week chemotherapy protocol would be associated with satisfactory treatment outcome in dogs with lymphoma. ANIMALS: 77 dogs with histologically or cytologically confirmed diagnosis of lymphoma. METHODS: Prospective clinical trial in which dogs were treated with a 12-week chemotherapy protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and prednisolone. RESULTS: Complete remission rate was 76.3%. Multivariate logistic regression analysis revealed that clinical substage (P = .006) and immunophenotype (P = .003) had a significant influence on the likelihood of a dog achieving complete remission. Median duration of first complete remission was 243 days (range 19-1,191 days). The 6-month, 1-year, and 2-year remission rates were 68%, 28%, and 16%, respectively. In the multivariate analysis of patient variables, immunophenotype (P = .022) revealed a significant influence on first remission duration. Toxicosis was mild with the exception of 1 treatment-associated death. CONCLUSIONS AND CLINICAL IMPORTANCE: In this group of dogs the 12-week maintenance-free chemotherapy protocol was well tolerated and had satisfactory results.     

Evaluation of a high-dose chemotherapy protocol with no maintenance therapy for dogs with lymphoma

The purpose of this study was to evaluate the efficacy and toxicity of an intensified dose protocol with no maintenance phase for the treatment of canine lymphoma. Forty-nine dogs all weighing more than 15 kg were entered. Dogs were staged and treated with a modified version of the University of Wisconsin (UW)-Madison protocol for lymphoma. Modifications included increased dosages of cyclophosphamide (250 mg/m² compared to 200 mg/m²) and doxorubicin (37.5 mg/m² compared to 30 mg/m²), with no crossover to chlorambucil or methotrexate. After 25 weeks on protocol (17 treatments), therapy was discontinued and dogs were monitored for relapse on a monthly basis. Disease-free interval (DFI) and overall survival were compared to 55 historical controls treated with the UW-Madison protocol. The 2 groups were comparable with respect to age, sex, breed, stage, presence of hypercalcemia, and CD3 status; a trend toward more substage b dogs was present in the high-dose group ( P = .076). When comparing response rate, DFI, death due to disease, and death due to treatment-related toxicity, more dogs were dead due to toxicity ( P < .001; odds ratio = 8.8) in the high-dose group. Overall survival between the high-dose and control groups did not differ significantly ( P = .55) at 270 and 318 days, respectively. The intensified dose protocol is an option for owners who are willing to risk higher toxicity for a shorter protocol with no statistical difference in survival from the UW-Madison protocol.     

Detection of oligoclonal bands in cerebrospinal fluid from German Shepherd dogs with degenerative myelopathy by isoelectric focusing and immunofixation

BACKGROUND: Detection of intrathecal IgG synthesis is important in evaluating inflammatory diseases in the central nervous system. Isoelectric focusing (IEF) is currently the most sensitive method to demonstrate intrathecal IgG synthesis and may have diagnostic value for German Shepherd degenerative myelopathy (GSDM). OBJECTIVE: The objective of this study was to adapt a modified IEF and immunofixation method for the detection of oligoclonal bands in cerebrospinal fluid (CSF) from dogs with GSDM. METHODS: Serum and lumbar CSF samples were collected from 6 German Shepherd dogs clinically diagnosed with GSDM. Samples were also collected from 6 clinically healthy dogs for comparison. The concentration of IgG was measured by quantitative ELISA and the concentration of total protein was measured by the Bradford protein assay. The presence of oligoclonal bands was evaluated by use of modified IEF followed by immunofixation. RESULTS: The concentrations of total protein and IgG, and the IgG/total protein ratio in CSF samples, were not significantly different between GSDM patients and control dogs. Four GSDM patients had oligoclonal bands in their CSF based on IEF-immunofixation. No oligoclonal bands were found in CSF from control dogs. CONCLUSION: The results suggest that the detection of oligoclonal bands by IEF-immunofixation may have diagnostic value for GSDM, and support the idea that humoral immune responses may play a role in the pathogenesis of GSDM.     

Progressive ataxia associated with degenerative thoracic myelopathy in Merino sheep

A neurological disorder in Merino sheep, characterised clinically by progressive posterior ataxia and microscopically by Wallerian degeneration in thoracic segments of the spinal cord, is described. Animals of both sexes were affected, with the earliest onset of disease being at 5 months of age. Most affected animals died before 2 years of age. The clinical, pathological and epidemiological features suggest that this degenerative thoracic myelopathy is a previously unrecognised entity differing from other reported causes of ataxia in sheep in Australia.     

Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma

The purpose of this study was to compare a maintenance-free chemotherapy protocol based on CHOP (H from hydroxydaunorubicin = doxorubicin, O from Oncovin = vincristine) to a similar protocol with a maintenance phase for the treatment of canine lymphoma. Fifty-three dogs with multicentric lymphoma were treated with a 6-month modified version of the University of Wisconsin (UW)-Madison chemotherapy protocol (UW-25). Disease-free interval (DFI) and survival were compared to a historical control group of 55 dogs treated with a similar protocol with a prolonged maintenance phase. Remission rate for the study dogs was 94.2% (complete remission = 92.3%, partial remission = 1.9%). DFI and survival between the 2 groups did not differ significantly, with median DFI and survival of the study dogs equal to 282 and 397 days compared to 220 and 303 days for the control dogs (P = .2835 and .3365, respectively). Univariate analysis identified substage b (P = .0087), German Shepherd breed (P = .0199), and body weight > 18 kg (P = .0016) as significant for worse survival. Longer survival was associated with thrombocytopenia (P = .0436). Multivariate analysis revealed that substage (P = .0388) and weight (P = .0125) retained significance for DFI, whereas substage (P = .0093), thrombocytopenia (P = .0150), and weight (P = 0 .0050) retained significance for survival. Overall, the protocol was well tolerated by the dogs, with 41.5% (22/53) requiring a treatment delay or dose modification, but only 9.4% (5/53) needing hospitalization. The 6-month chemotherapy protocol based on CHOP with no maintenance phase provides similar DFI and survival times when compared to a similar protocol with a prolonged maintenance phase.     

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.     

Evaluation of the results of a L-asparaginase-based continuous chemotherapy protocol versus a short doxorubicin-based induction chemotherapy protocol in dogs with malignant lymphoma.

The results of an L-asparaginase-based continuous chemotherapy protocol (n = 52) versus a short doxorubicin-based induction chemotherapy protocol (n = 65) were evaluated in 117 dogs with malignant lymphoma. There were no differences between the two groups in patient characteristics or incidence of protocol-related toxicity. Complete remission was induced in 71.2% of the dogs treated with the L-asparaginase protocol and in 67.7% of the dogs treated with the doxorubicin-plus protocol. The calculated Kaplan-Meier one- and two-year survival fractions in the L-asparaginase group were 48% and 26%, and in the doxorubicin-plus group 35%, and 22%, respectively. Differences in remission and survival between the two treatment groups were not significant. A multivariate Cox proportional hazards survival analysis revealed that elevated pretreatment plasma creatinine concentration and prior treatment with prednisolone were associated with shorter survival times. An elevated pretreatment plasma creatinine concentration and total leucocyte count were associated with a decrease in the disease-free period. Differences in efficacy and toxicity between the two protocols were not significant. There is no apparent advantage in using the continuous L-asparaginase protocol, and the shorter doxorubicin-plus protocol is less expensive and less time consuming.     

Possible therapeutic benefits of adenosine-potentiating drugs in reducing age-related degenerative disease in dogs and cats

Adenosine is a ubiquitous, biologically important molecule that is a precursor of other biologically active molecules. It also is a component of some co-factors and has distinct physiological actions in its own right. Levels are maintained by synthesis from dietary precursors and re-cycling. The daily turnover of adenosine is very high. Adenosine can act either as a hormone by binding to adenosine receptors, four adenosine receptor subtypes have been identified, and as an intracellular modulator, after transport into the cell by membrane transporter proteins. One of the principal intracellular actions of adenosine is inhibition of the enzyme phosphodiesterase. Extracellular adenosine also has specific neuromodulatory actions on dopamine and glutamate. Selective and nonselective agonists and antagonists of adenosine are available. The tasks of developing, evaluating and exploiting the therapeutic potential of these compounds is still in its infancy. Adenosine has actions in the central nervous system (CNS), heart and vascular system, skeletal muscle and the immune system and the presence of receptors suggests potential actions in the gonads and other organs. Adenosine agonists improve tissue perfusion through actions on vascular smooth muscle and erythrocyte fluidity and they can be used to improve the quality of life in aged dogs. This article reviews the therapeutic potential of adenosine-potentiating drugs in the treatment of age-related conditions in companion animals, some of which may be exacerbated by castration or spaying at an early age.     

Fibrocartilaginous embolic myelopathy in dogs: a retrospective study

The clinical aspects of 26 dogs suspected of fibrocartilaginous embolic myelopathy (FEM) were documented and compared to results from 2 studies published in the literature. The short-term recovery capacity of 15 of these patients was also evaluated during a 30 day period by giving a neurological score. We have observed, compared to other studies, a larger proportion of cervical localization (15.4%) as well as a larger variety of race sizes for FEM. We have established that, after 30 days, 67% of patients had improved and that 88% of non-ambulatory patients had regained their ambulatory capacity. Also, patients showing signs of grey matter lesions (inferior motor neuron--IMN) as well as those having white matter lesions (superior motor neuron--SMN) had shown signs of neurological progress. Therefore, we have observed that the recovery capacity of an animal suffering from FEM does not seem to be impacted by its initial ambulatory state, nor by its lesions to IMN or SMN, although the low number of cases does not allow us to positively confirm this situation.     

Immunohistochemical evidence for immunoglobulin and complement deposition in spinal cord lesions in degenerative myelopathy in German shepherd dogs.

The purpose of this study was to examine the distribution of immunoglobulin and complement component C3 in spinal cord tissues of dogs with degenerative myelopathy. Sections of formalin-fixed paraffin-embedded spinal cord from five German Shepherd dogs with clinical and histological features consistent with degenerative myelopathy (DM) and one normal dog were tested immunohistochemically for deposition of immunoglobulin G (IgG) and the third component of complement (C3). In all dogs there was staining associated with large and small blood vessels. In addition, in the dogs with DM there was focal staining for IgG and C3 in spinal nerve tracts characteristically affected in DM. Deposition of IgG and C3 was found in histological lesions, and in addition, in other areas independent of visible lesions, suggesting that IgG and C3 deposition may precede histological evidence of spinal cord damage. These findings suggest a role for immune-mediated destruction of the spinal cord which may contribute to the pathogenesis of DM in German Shepherd dogs.     

Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short-term single-agent protocol in dogs with lymphoma

OBJECTIVE: To compare response rates and remission and survival times in dogs with lymphoma treated with a continuous, multiagent, doxorubicin-based chemotherapeutic protocol or with a short-term single-agent protocol incorporating doxorubicin. DESIGN: Nonrandomized controlled clinical trial. ANIMALS: 114 dogs with lymphoma. PROCEDURES: Dogs were treated with a chemotherapeutic protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate, and prednisolone (n=87) or doxorubicin alone (27). RESULTS: 63 of 86 (73%) dogs treated with the multiagent protocol (data on response was unavailable for 1 dog) and 14 of 27 (52%) dogs treated with the single-agent protocol had a complete remission. Dogs with lymphoma classified as substage相似文献