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Urinary incontinence (UI) is a disorder of micturition that can occur in dogs of any age, sex, and breed depending on the underlying cause and time of onset. Diagnosis and treatment for various causes of UI in dogs have been described by multiple comprehensive single author review articles, but large prospective clinical trials comparing treatment outcomes in veterinary medicine are lacking. The objectives of this consensus statement therefore are to provide guidelines on both recommended diagnostic testing and treatment for various causes of UI in dogs. Specifically, pathophysiology directly related to the canine urinary system will be reviewed and diagnostic and therapeutic challenges will be addressed. A panel of 12 experts in the field (8 small animal internists [L. Adams, J. Bartges, A. Berent, J. Byron, J. Foster, A. Kendall, S. Vaden, J. Westropp], 2 neurologists [J. Coates, N. Olby], 1 radiologist [G. Oetelaar], and 1 surgeon [C. Adin]) was formed to assess and summarize evidence in the peer‐reviewed literature and to complement it with consensus recommendations using the Delphi method. Some statements were not voted on by all panelists. This consensus statement aims to provide guidance for management of both male and female dogs with underlying storage or voiding disorders resulting in UI.

Background Antemortem diagnosis of degenerative myelopathy (DM) in dogs is presumptive and there are no accepted guidelines for the management of this condition. Hypothesis/Objectives Describe current practices of neurology clinicians and physical rehabilitation professionals in the diagnosis and management of DM. Animals None. Methods Online surveys examining diagnosis and management of DM were constructed and distributed via neurology and rehabilitation listservs. Results One hundred ninety neurology and 79 rehabilitation professionals from 20 countries participated. Most neurology (142/189) and rehabilitation (23/39) respondents required genetic testing for the superoxide dismutase 1 (SOD1) mutation and 82/189 neurologists also required spinal magnetic resonance imaging (MRI) for presumptive DM diagnosis. Most neurology respondents recommended exercise (187/190) and physical rehabilitation (184/190). Over 50% (102/190) of neurology respondents perform rechecks on dogs diagnosed with DM. Rehabilitation respondents reported preservation or improvement of strength (78/79) and coordination (77/79) as therapeutic goals. At‐home exercises (75/79), underwater treadmill (64/79), gait training (55/79), and strength building exercises (65/79) were used to maintain strength (58/79), coordination (56/79), muscle mass (56/79), and improve overall wellbeing (54/79). Neurology respondents reported that owners elect euthanasia when dogs become nonambulatory paraparetic whereas rehabilitation respondents report euthanasia when paraplegia and incontinence develop. Conclusion and Clinical Importance The majority of dogs diagnosed with DM have not undergone advanced imaging, the combination of history, neurological findings, and genetic testing is heavily relied upon. Whereas the diagnosis of DM is frequently made by veterinary neurologists, continued care is often performed by rehabilitation professionals or primary veterinarians.

Dystrophin-deficient dogs are by far the best available large animal models for Duchenne muscular dystrophy (DMD), the most common lethal childhood muscle degenerative disease. The use of the canine DMD model in basic disease mechanism research and translational studies will be greatly enhanced with the development of reliable outcome measures. Electrical impedance myography (EIM) is a non-invasive painless procedure that provides quantitative data relating to muscle composition and histology. EIM has been extensively used in neuromuscular disease research in both human patients and rodent models. Recent studies suggest that EIM may represent a highly reliable and convenient outcome measure in DMD patients and the mdx mouse model of DMD. To determine whether EIM can be used as a biomarker of disease severity in the canine model, we performed the assay in fourteen young (~6.6-m-old; 6 normal and 8 affected) and ten mature (~16.9-m-old; 4 normal and 6 affected) dogs of mixed background breeds. EIM was well tolerated with good inter-rater reliability. Affected dogs showed higher resistance, lower reactance and phase. The difference became more straightforward in mature dogs. Importantly, we observed a statistically significant correlation between the EIM data and muscle fibrosis. Our results suggest that EIM is a valuable objective measurement in the canine DMD model.

Targeting of the CB2 receptor results in neuroprotection in the SOD1G93A mutant mouse model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors are facilitated by their upregulation in the spinal cord of the mutant mice. Here, we investigated whether similar CB2 receptor upregulation, as well as parallel changes in other endocannabinoid elements, is evident in the spinal cord of dogs with degenerative myelopathy (DM), caused by mutations in the superoxide dismutase 1 gene (SOD1). We used well-characterized post-mortem spinal cords from unaffected and DM-affected dogs. Tissues were used first to confirm the loss of motor neurons using Nissl staining, which was accompanied by glial reactivity (elevated GFAP and Iba-1 immunoreactivity). Next, we investigated possible differences in the expression of endocannabinoid genes measured by qPCR between DM-affected and control dogs. We found no changes in expression of the CB1 receptor (confirmed with CB1 receptor immunostaining) or NAPE-PLD, DAGL, FAAH and MAGL enzymes. In contrast, CB2 receptor levels were significantly elevated in DM-affected dogs determined by qPCR and western blotting, which was confirmed in the grey matter using CB2 receptor immunostaining. Using double-labelling immunofluorescence, CB2 receptor immunolabelling colocalized with GFAP but not Iba-1, indicating upregulation of CB2 receptors on astrocytes in DM-affected dogs. Our results demonstrate a marked upregulation of CB2 receptors in the spinal cord in canine DM, which is concentrated in activated astrocytes. Such receptors could be used as a potential target to enhance the neuroprotective effects exerted by these glial cells.

Canine degenerative myelopathy (DM) is a naturally occurring neurodegenerative disease with similarities to some forms of amyotrophic lateral sclerosis (ALS). Most dogs that develop DM are homozygous for a common superoxide dismutase 1 gene (SOD1) mutation. However, not all dogs homozygous for this mutation develop disease. We performed a genome-wide association analysis in the Pembroke Welsh Corgi (PWC) breed comparing DM-affected and -unaffected dogs homozygous for the SOD1 mutation. The analysis revealed a modifier locus on canine chromosome 25. A haplotype within the SP110 nuclear body protein (SP110) was present in 40% of affected compared with 4% of unaffected dogs (P = 1.5 × 10−5), and was associated with increased probability of developing DM (P = 4.8 × 10−6) and earlier onset of disease (P = 1.7 × 10−5). SP110 is a nuclear body protein involved in the regulation of gene transcription. Our findings suggest that variations in SP110-mediated gene transcription may underlie, at least in part, the variability in risk for developing DM among PWCs that are homozygous for the disease-related SOD1 mutation. Further studies are warranted to clarify the effect of this modifier across dog breeds.

Background Degenerative myelopathy (DM) in dogs shares similarities with superoxide dismutase 1‐associated human amyotrophic lateral sclerosis (ALS). Brain microstructural lesions are quantified using diffusion tensor imaging (DTI) in ALS patients. Objective Characterize brain neurodegenerative changes in DM‐affected dogs using DTI. Animals Sixteen DM‐affected and 8 control dogs. Methods Prospective observational study. Brain DTI was performed at baseline and every 3 months on DM‐affected dogs and compared to controls. Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated on specified regions of interest. Gait scores (0, normal to 14, tetraplegia) were assigned at each scan. Diffusion tensor imaging values in DM‐affected dogs were compared to controls, gait scores, and evaluated over time. Results Mean age was 5.7 years (SD 3.2) in controls and 9.7 years (SD 1.4) in DM‐affected dogs. In DM‐affected dogs, mean baseline gait score was 4 (SD 1), and mean score change from baseline to last scan was 4.82 (SD 2.67). Nine dogs had ≤3 scans; 7 had >3 scans. Accounting for age, no differences in DTI indices were identified for any brain or proximal spinal cord regions between DM‐affected dogs and controls (P > .05). Diffusion tensor imaging values poorly correlated with gait scores (R2 < .2). No significant changes were identified in diffusion indices over time (P > .05). Conclusions and Clinical Importance Diffusion tensor imaging indices did not differentiate DM‐affected from control dogs, detect longitudinal changes, or differentiate disease severity. Findings do not yet support brain DTI as an imaging biomarker.

Background The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail. Objectives To compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in dogs. Animals Client‐owned dogs (n = 44) with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus. Methods Randomized parallel group clinical trial. Patients were randomly allocated to the IN‐MDZ (n = 21) or IV‐MDZ (n = 23) group. Number of successfully treated cases (defined as seizure cessation within 5 minutes and lasting for ≥10 minutes), seizure cessation time, and adverse effects were recorded. Comparisons were performed using the Fisher's exact and Wilcoxon rank sum tests with statistical significance set at α < .05. Results IN‐MDZ and IV‐MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively (P = .34). The median seizure cessation time was 33 and 64 seconds for IN‐MDZ and IV‐MDZ, respectively (P = .63). When the time to place an IV catheter was taken into account, IN‐MDZ (100 seconds) was superior (P = .04) to IV‐MDZ (270 seconds). Sedation and ataxia were seen in 88% and 79% of the dogs treated with IN‐MDZ and IV‐MDZ, respectively. Conclusions and Clinical Importance Both routes are quick, safe, and effective for controlling status epilepticus. However, the IN route demonstrated superiority when the time needed to place an IV catheter was taken into account.

While a necessary step toward enhancing rigor and reproducibility of veterinary clinical trials conducted on the translational spectrum includes understanding the current state of the field, no broad assessment of existing veterinary clinical trial resources has been previously conducted. Funded by a CTSA One Health Alliance (COHA) pilot award, the goal of this project was to conduct an electronic survey of North American Veterinary Colleges regarding practices in veterinary clinical trial review, approval, conduct, and support in order to identify opportunities to leverage existing resources and develop new ones to enhance the impact of veterinary and translational health research. A total of 30 institutions were invited to participate in the survey and the survey response rate was 73 %. The most common source of funding noted for veterinary clinical research was industry (33 %); however, respondents reported that only 5 % (3.7–11.0) of studies were FDA-regulated. Respondents indicated that most studies (80 %); conducted at their institution were single site studies. Study review and approval involved the IACUC either solely, or in combination with a hospital review board, at 95.5 % of institutions. Workforce training related to clinical research best practices was variable across institutions. Opportunities were identified to strengthen infrastructure through harmonization of clinical research review and approval practices. This might naturally lead to expansion of multi-site studies. Based on respondent feedback, future workforce development initiatives might center on training in the specifics of conducting FDA-sponsored research, Good Clinical Practice (GCP), clinical study budget design, grants management, adverse event reporting, study monitoring and use of electronic data capture platforms.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons and grim prognosis. Over the last decade, studies on neurodegenerative diseases pointed on the role of glia in supporting the proper function of neurons. Particularly, oligodendrocytes were shown to be essential through myelin production and supplying axons with energy metabolites via monocarboxylate transporters (MCT). We have used dogs with naturally occurring degenerative myelopathy (DM) which closely resembles features observed in human ALS. We have performed two types of analysis of spinal cord tissue samples: histology and molecular analysis. Histology included samples collected from dogs that succumbed to the DM at different disease stages, which were compared to age-matched controls as well as put in the context of young spinal cords. Molecular analysis was performed on spinal cords with advanced DM and age-matched samples and included real-time PCR analysis of selected gene products related to the function of neurons, oligodendrocytes, myelin, and MCT. Demyelination has been detected in dogs with DM through loss of eriochrome staining and decreased expression of genes related to myelin including MBP, Olig1, and Olig2. The prominent reduction of MCT1 and MCT2 and increased MCT4 expression is indicative of disturbed energy supply to neurons. While Rbfox3 expression was not altered, the ChAT production was negatively affected. DM in dogs reproduces main features of human ALS including loss of motor neurons, dysregulation of energy supply to neurons, and loss of myelin, and as such is an ideal model system for highly translational studies on therapeutic approaches for ALS.

The goal of this study was to compare dysphagia phenotypes in low and high copy number (LCN and HCN) transgenic superoxide dismutase 1 (SOD1) mouse models of ALS to accelerate the discovery of novel and effective treatments for dysphagia and early amyotrophic lateral sclerosis (ALS) diagnosis. Clinicopathological features of dysphagia were characterized in individual transgenic mice and age-matched controls utilizing videofluoroscopy in conjunction with postmortem assays of the tongue and hypoglossal nucleus. Quantitative PCR accurately differentiated HCN-SOD1 and LCN-SOD1 mice and nontransgenic controls. All HCN-SOD1 mice developed stereotypical paralysis in both hindlimbs. In contrast, LCN-SOD1 mice displayed wide variability in fore- and hindlimb involvement. Lick rate, swallow rate, inter-swallow interval, and pharyngeal transit time were significantly altered in both HCN-SOD1 and LCN-SOD1 mice compared to controls. Tongue weight, tongue dorsum surface area, total tongue length, and caudal tongue length were significantly reduced only in the LCN-SOD1 mice compared to age-matched controls. LCN-SOD1 mice with lower body weights had smaller/lighter weight tongues, and those with forelimb paralysis and slower lick rates died at a younger age. LCN-SOD1 mice had a 32% loss of hypoglossal neurons, which differed significantly when compared to age-matched control mice. These novel findings for LCN-SOD1 mice are congruent with reported dysphagia and associated tongue atrophy and hypoglossal nucleus pathology in human ALS patients, thus highlighting the translational potential of this mouse model in ALS research.