Dystrophin-Deficient Muscular Dystrophy in Two Male Juvenile Brittanys.

A 6 mo old and a 7 mo old male intact Brittany were presented for progressive exercise intolerance, failure to grow, and dysphagia. Creatine kinase activity was markedly and persistently elevated in both dogs. Based on the neurological examination, clinical signs localized to the neuromuscular system. Electromyography revealed complex repetitive discharges in multiple muscle groups. Immunofluorescence of biopsies confirmed dystrophin-deficient muscular dystrophy. This is the first report describing dystrophin-deficient muscular dystrophy in the Brittany breed. Currently, no specific therapies are available for this form of myopathy. The presence of dystrophin deficiency in the two dogs suggests an inherited myopathy rather than a spontaneous mutation. The location of the dogs in the United States and Japan suggests a wide distribution of this dystrophy and should alert clinicians to the existence of this myopathy in the Brittany breed. A mutation in the DMD gene has not yet been identified.

Lysosomal storage disease associated with a CNP sequence variant in Dalmatian dogs.

A progressive neurological disorder was identified in purebred Dalmatian dogs. The disease is characterized by anxiety, pacing and circling, hypersensitivity, cognitive decline, sleep disturbance, loss of coordination, loss of control over urination and defecation, and visual impairment. Neurological signs first became apparent when the dogs were approximately 18 months of age and progressed slowly. Two affected littermates were euthanized at approximately 7 years, 5 months and 8 years, 2 months of age due to the severity of neurological impairment. The mother of the affected dogs and four other relatives exhibited milder, later-onset neurological signs. Pronounced accumulations of autofluorescent intracellular inclusions were found in cerebral cortex, cerebellum, optic nerve, and cardiac muscle of the affected dogs. These inclusions co-localized with immunolabeling of the lysosomal marker protein LAMP2 and bound antibodies to mitochondrial ATPase subunit c, indicating that the dogs suffered from a lysosomal storage disease with similarities to the neuronal ceroid lipofuscinoses. Ultrastructural analysis indicated that the storage bodies were surrounded by a single-layer membrane, but the storage granules were distinct from those reported for other lysosomal storage diseases. Whole genome sequences, generated with DNA from the two euthanized Dalmatians, both contained a rare, homozygous single-base deletion and reading-frame shift in CNP which encodes the enzyme CNPase (EC 3.1.4.37). The late-onset disease was exhibited by five of seven related Dalmatians that were heterozygous for the deletion allele and over 8 years of age, whereas none of 16 age-matched reference-allele homozygotes developed neurologic signs. No CNPase antigen could be detected with immunohistochemical labeling in tissues from the dogs with the earlier-onset disorder. Similar to the later-onset Dalmatians, autofluorescent storage granules were apparent in brain and cardiac tissue from transgenic mice that were nullizygous for Cnp. Based on the clinical signs, the histopathological, immunohistochemical, ultrastructural, and molecular-genetic findings, and the finding that nullizygous Cnp mice accumulate autofluorescent storage granules, we propose that the earlier-onset Dalmatian disorder is a novel lysosomal storage disease that results from a loss-of-function mutation in CNP and that shares features characteristic of the neuronal ceroid lipofuscinoses. That the later-onset disorder occurred only in dogs heterozygous for the CNP deletion variant suggests that this disorder is a result of the variant allele's presence.

Clinical features and outcome of acquired myasthenia gravis in 94 dogs.

BACKGROUND: Factors known to be associated with outcome of acquired myasthenia gravis (MG) in dogs are limited. HYPOTHESIS/OBJECTIVES: Of dogs with MG, advancing age and comorbid neoplasia are associated with poor long-term prognosis and low rates of remission. ANIMALS: Ninety-four client-owned dogs with MG diagnosed by acetylcholine receptor antibody (AChR Ab) assay between 2001 and 2019 from a university clinic and 3 private clinics in the United States. METHODS: Cases were retrospectively evaluated and data were collected to determine clinical signs, treatment, and response to therapy defined by means of a clinical scoring rubric. Immunological remission was defined as a return of the AChR Ab concentration to <0.6 nmol/L. Multivariable binary logistic regression analysis was used to identify clinical criteria predicting remission. RESULTS: An anticholinesterase drug was used to treat 90/94 (96%) dogs, which in 63/94 (67%) was the sole treatment; other drugs included immune modulators. Clinical remission (lack of clinical signs ≥4 weeks after treatment cessation) was observed in 29 (31% [95% confidence interval (CI): 22.4-40.8%]) dogs, clinical response (lack of clinical signs on treatment) in 14 (15% [95% CI: 9.0-23.6%]) dogs, clinical improvement (on treatment) in 24 (26% [95% CI: 17.8-35.2%]) dogs, and no clinical improvement in 27 (29% [95% CI: 20.5-38.6%]) dogs. Immunological remission was observed in 27/46 (59%) dogs, with clinical remission in all 27. Younger age (P = .04) and comorbid endocrine disease (P = .04) were associated with clinical remission. Initial AChR Ab concentration (P = .02) and regurgitation (P = .04) were negatively associated with clinical remission. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical remission in MG is less likely in older dogs and dogs presenting with regurgitation or high initial AChR Ab concentration, but more likely in younger dogs and dogs with comorbid endocrine disease.

Myeloid-derived suppressor cell and regulatory T cell frequencies in canine myasthenia gravis: A pilot study.

Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated autoimmune disease. Little is known about its cellular pathogenesis in dogs. This study provides the first preliminary assessment of the frequency of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the peripheral blood of dogs with seropositive generalized MG. No alteration in frequency of either MDSCs or Tregs in dogs with MG was observed when compared to those in either seronegative dogs with diagnoses other than MG, or healthy dogs. A longitudinal study in three dogs with MG revealed no correlation between the relative numbers of either population and the clinical course of disease. Neither the frequency of MDSCs nor of Tregs showed a correlation with anti-AChR antibody titer in dogs with MG. These findings suggest that aberrations in the frequency of either immunosuppressive population do not occur in MG, but they need to be validated in large-scale prospective studies.

Case Report: Mineralized Pulmonary Artery Thrombi in Two Dogs Treated for Meningoencephalitis of Unknown Origin.

Meningoencephalitis of unknown origin (MUO) is a relatively common and very serious canine neurologic condition, which is typically associated with a poor long term prognosis despite treatment. This case series chronicles two dogs diagnosed with MUO who were treated with long term corticosteroids and cytosine arabinoside and lived well-beyond the typical survival time for this condition. Both eventually succumbed to respiratory signs associated with mineralized thrombi in their pulmonary arteries. Adverse effects from the two drugs used for treatment are reviewed in order to propose a possible mechanism to explain how long term use of these medications could result in such a phenomenon.