Frameshift Variant in AMPD2 in Cirneco dell'Etna Dogs with Retinopathy and Tremors.

While the manifestations of many inherited retinal disorders are limited to loss of vision, others are part of a syndrome that affects multiple tissues, particularly the nervous system. Most syndromic retinal disorders are thought to be recessively inherited. Two dogs out of a litter of Cirneco dell' Etna dogs, both males, showed signs of retinal degeneration, along with tremors and signs described as either atypical seizures or paroxysmal dyskinesias, while the other two male littermates were normal. We named this oculo-neurological syndrome CONS (Cirneco oculo-neurological syndrome), and undertook homozygosity mapping and whole-genome sequencing to determine its potential genetic etiology. Notably, we detected a 1-bp deletion in chromosome 6 that was predicted to cause a frameshift and premature stop codon within the canine AMPD2 gene, which encodes adenosine monophosphate deaminase, an enzyme that converts adenosine 5'-monophosphate (AMP) to inosine 5'-monophosphate (IMP). Genotyping of the available Cirneco population suggested perfect segregation between cases and controls for the variant. Moreover, this variant was absent in canine genomic databases comprised of thousands of unaffected dogs. The AMPD2 genetic variant we identified in dogs presents with retinal manifestations, adding to the spectrum of neurological manifestations associated with AMPD2 variants in humans.

Clinical features of muscle stiffness in 37 dogs with concurrent naturally occurring hypercortisolism.

BACKGROUND: Severe muscle stiffness (SMS) in dogs with hypercortisolism (HC) is uncommon. OBJECTIVES: To evaluate signalment, presentation, treatments, and long-term outcomes of dogs with concurrent HC and SMS. ANIMALS: Thirty-seven dogs. METHODS: Medical records of dogs with HC and concurrent SMS were recruited from 10 institutions. Clinical information, test results, therapeutic responses, and survival times were reviewed. RESULTS: All 37 dogs with HC and SMS had pituitary-dependent hypercortisolism (PDH); 36/37 weighed <20 kg. Signs and test results were typical of PDH aside from SMS, initially diagnosed in all 4 limbs in 9, pelvic limbs of 22, and thoracic limbs of 6 dogs. Hypercortisolism and SMS were diagnosed together in 3 dogs; HC 1-36 months before SMS in 23; SMS 1-12 months before HC in 11. Mitotane or trilostane, given to control HC in 36/37 dogs, improved or resolved HC signs in 28; SMS did not resolve, remaining static or worsening in 31/36 dogs, mildly improving in 5/19 dogs given additional therapies. Progression of SMS included additional limbs in 10 dogs and the masticatory muscles of 2. The median survival time from diagnosis of SMS was 965 days (range, 8-1188). CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent SMS and HC is uncommon, possibly affecting only dogs with PDH. Development of SMS might occur before or after diagnosis of HC. Apart from SMS, the clinical picture and survival time of these dogs seem indistinguishable from those of dogs with HC in general. However, while muscle weakness usually resolves with HC treatment SMS does not.

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.

Pasteurella Multocida meningoencephalomyelitis in a dog secondary to severe periodontal disease.

Pasteurella multocida can cause meningoencephalomyelitis in canine patients with severe periodontal disease. Fever and neutrophilic pleocytosis in the cerebrospinal fluid are likely, and blood culture and/or empiric antibiotic therapy are indicated.

Comparison between cerebrospinal fluid and serum lactate concentrations in neurologic dogs with and without structural intracranial disease.

The objectives of this study were to investigate the relationship between cerebrospinal fluid lactate and serum concentrations in dogs with clinical signs of central nervous system disease and to establish if cerebrospinal fluid lactate (CSF) concentrations are higher in dogs with structural intracranial disease (Group Pos-MRI) compared to dogs that have clinical signs of intracranial disease but no structural brain disease (Group Neg-MRI) based on magnetic resonance imaging (MRI) findings. Using a prospective study canine blood and cerebrospinal fluid were collected in 24 dogs with neurological signs after undergoing brain MRI. Dogs were divided in 2 groups. No significant difference between serum lactate (1.57 ± 0.9 mmol/L) and CSF lactate concentration (1.34 ± 0.3 mmol/L) was detected. There was a direct correlation between CSF and serum lactate concentration (R = 0.731; P = 0.01). No significant difference was found in CSF lactate concentration between the 2 groups of dogs (P = 0.13).

Les objectifs de la présente étude étaient d'examiner la relation entre les concentrations de lactate du liquide céphalo-rachidien (LCR) et du sérum chez des chiens présentant des signes cliniques de pathologie du système nerveux central et établir si les concentrations de lactate du LCR sont plus élevées chez les chiens avec une maladie intracrânienne structurale (Groupe Pos-IRM) comparativement à des chiens avec des signes cliniques de maladie intracrânienne mais sans maladie structurale du cerveau (Groupe Nég-IRM) sur la base des trouvailles en imagerie par résonnance magnétique (IRM). Utilisant une étude prospective, du sang canin et du LCR ont été prélevés chez 24 chiens avec des signes neurologiques après un examen par IRM du cerveau. Les chiens ont été séparés en deux groupes. Aucune différence significative ne fut détectée entre les concentrations de lactate sérique (1,57 ± 0,9 mmol/L) et de lactate du LCR (1,34 ± 0,3 mmol/L). Il y avait une corrélation directe entre les concentrations de lactate du LCR et du sérum (R = 0,731; P = 0,01). Aucune différence significative dans la concentration de lactate du LCR ne fut trouvée entre les deux groupes de chiens (P = 0,13).(Traduit par Docteur Serge Messier).

Retrospective cohort study on the incidence of acute kidney injury and death following hydroxyethyl starch (HES 10% 250/0.5/5:1) administration in dogs (2007-2010).

OBJECTIVE: To determine the incidence of in-hospital adverse outcomes including acute kidney injury (AKI) and death in a population of dogs admitted to the intensive care unit (ICU) receiving 10% hydroxyethyl starch (HES) [250/0.5/5:1] compared with the general ICU population, while controlling for illness severity. DESIGN: Cohort study conducted between January 2007 and March 2010. SETTING: Veterinary teaching hospital. ANIMALS: Consecutive sample of dogs receiving HES (n = 180) were compared with a randomly selected sample of dogs (n = 242) admitted to the ICU over the same period. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: AKI was defined as an at least 2-fold increase in baseline creatinine concentration or new onset of oliguria/anuria persisting for ≥12 hours. The primary outcome was a composite of in-hospital death or AKI. Unadjusted and adjusted analysis controlling for illness severity using the acute patient physiologic and laboratory evaluation (APPLEfast ) score and other confounders was performed. HES was administered either as incremental boluses (median dose 8.2 mL/kg/day, interquartile range [IQR] 5.0-11.3 mL/kg/day) or as a continuous rate infusion (CRI; median dose 26mL/kg/day, IQR 24.0-48 mL/kg/day). In unadjusted analysis, HES administration was associated with increased risk of mortality (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.51-3.58, P < 0.001) or AKI (OR = 3.87, 95% CI = 1.21-12.37, P = 0.02). In an adjusted analysis after controlling for illness severity, admission type, and concurrent administration of blood products, HES administration remained an independent risk factor for the composite adverse outcome (OR = 1.98, 95% CI = 1.22-3.22, P = 0.005), with a number needed to harm (NNH) = 6 (95% CI = 4-23). CONCLUSIONS: HES therapy is associated with increased risk of an adverse outcome including death or AKI in dogs. A randomized controlled trial investigating the safety of HES therapy in canine patients is warranted.