Whole Genome Sequencing Indicates Heterogeneity of Hyperostotic Disorders in Dogs

Craniomandibular osteopathy (CMO) and calvarial hyperostotic syndrome (CHS) are proliferative, non-neoplastic disorders affecting the skull bones in young dogs. Different forms of these hyperostotic disorders have been described in many dog breeds. However, an incompletely dominant causative variant for CMO affecting splicing of SLC37A2 has been reported so far only in three Terrier breeds. The purpose of this study was to identify further possible causative genetic variants associated with CHS in an American Staffordshire Terrier, as well as CMO in seven affected dogs of different breeds. We investigated their whole-genome sequences (WGS) and filtered variants using 584 unrelated genomes, which revealed no variants shared across all affected dogs. However, filtering for private variants of each case separately yielded plausible dominantly inherited candidate variants in three of the eight cases. In an Australian Terrier, a heterozygous missense variant in the COL1A1 gene (c.1786G>A; p.(Val596Ile)) was discovered. A pathogenic missense variant in COL1A1 was previously reported in humans with infantile cortical hyperostosis, or Caffey disease, resembling canine CMO. Furthermore, in a Basset Hound, a heterozygous most likely pathogenic splice site variant was found in SLC37A2 (c.1446+1G>A), predicted to lead to exon skipping as shown before in SLC37A2-associated canine CMO of Terriers. Lastly, in a Weimaraner, a heterozygous frameshift variant in SLC35D1 (c.1021_1024delTCAG; p.(Ser341ArgfsTer22)) might cause CMO due to the critical role of SLC35D1 in chondrogenesis and skeletal development. Our study indicates allelic and locus heterogeneity for canine CMO and illustrates the current possibilities and limitations of WGS-based precision medicine in dogs

Whole Genome Sequencing Indicates Heterogeneity of Hyperostotic Disorders in Dogs

Craniomandibular osteopathy (CMO) and calvarial hyperostotic syndrome (CHS) are proliferative, non-neoplastic disorders affecting the skull bones in young dogs. Different forms of these hyperostotic disorders have been described in many dog breeds. However, an incompletely dominant causative variant for CMO affecting splicing of SLC37A2 has been reported so far only in three Terrier breeds. The purpose of this study was to identify further possible causative genetic variants associated with CHS in an American Staffordshire Terrier, as well as CMO in seven affected dogs of different breeds. We investigated their whole-genome sequences (WGS) and filtered variants using 584 unrelated genomes, which revealed no variants shared across all affected dogs. However, filtering for private variants of each case separately yielded plausible dominantly inherited candidate variants in three of the eight cases. In an Australian Terrier, a heterozygous missense variant in the COL1A1 gene (c.1786G>A; p.(Val596Ile)) was discovered. A pathogenic missense variant in COL1A1 was previously reported in humans with infantile cortical hyperostosis, or Caffey disease, resembling canine CMO. Furthermore, in a Basset Hound, a heterozygous most likely pathogenic splice site variant was found in SLC37A2 (c.1446+1G>A), predicted to lead to exon skipping as shown before in SLC37A2-associated canine CMO of Terriers. Lastly, in a Weimaraner, a heterozygous frameshift variant in SLC35D1 (c.1021_1024delTCAG; p.(Ser341ArgfsTer22)) might cause CMO due to the critical role of SLC35D1 in chondrogenesis and skeletal development. Our study indicates allelic and locus heterogeneity for canine CMO and illustrates the current possibilities and limitations of WGS-based precision medicine in dogs

Juvenile-onset polyneuropathy in American Staffordshire Terriers

Background: The only hereditary neurologic disorder described so far in American Staffordshire Terriers is adult-onset cerebellar degeneration secondary to ceroid lipofuscinosis. We have seen several dogs with a newly recognized neurological disease characterized by locomotor weakness with or without respiratory signs and juvenile onset consistent with degenerative polyneuropathy of genetic origin. Objectives: To characterize a novel polyneuropathy in juvenile American Staffordshire Terriers. Animals: Fourteen American Staffordshire Terriers presented with clinical signs consistent with juvenile-onset polyneuropathy at 5 veterinary hospitals between May 2005 and July 2017. Methods: Case series. Dogs were included retrospectively after a diagnosis of degenerative polyneuropathy had been confirmed by nerve biopsy. Clinical, pathological, electrophysiological, histological data, and outcome were reviewed and a pedigree analysis performed. Results: All dogs displayed clinical signs of neuromuscular disease with generalized motor and sensory involvement, associated with focal signs of laryngeal paralysis (10/14 dogs) and megaesophagus (1/14 dogs). Histopathological findings were consistent with degenerative polyneuropathy. Follow-up was available for 11 dogs, and 3 dogs were euthanized shortly after diagnosis. In these 11 dogs, the disease was slowly progressive and the animals maintained good quality of life with ability to walk. Pedigree analysis was mostly consistent with an autosomal recessive mode of inheritance. Conclusions and Clinical Importance: Juvenile polyneuropathy, associated with laryngeal paralysis, is a newly described entity in American Staffordshire Terriers, and results from degenerative neuropathy. When surgery for laryngeal paralysis is performed, lifespan may be similar to that of normal dogs even though affected dogs have locomotor disturbance

Relationship between magnetic resonance imaging findings and histological grade in spinal peripheral nerve sheath tumors in dogs

BackgroundPeripheral nerve sheath tumors (PNSTs) are a group of neoplasms originating from Schwann cells or pluripotent cell of the neural crest. Therapeutic options and prognosis are influenced by their degree of malignancy and location.Hypothesis/ObjectivesIdentify magnetic resonance imaging (MRI) features predictive of PNST histologic grade.AnimalsForty‐four dogs with histopathological diagnosis of spinal PNSTs and previous MRI investigation.MethodsA multicenter retrospective study including cases with (a) histopathologic diagnosis of PNST and (b) MRI studies available for review. Histologic slides were reviewed and graded by a board‐certified pathologist according to a modified French system (FNCLCC) for grading soft tissue sarcomas. The MRI studies were reviewed by 2 board‐certified radiologists blinded to the grade of the tumor and the final decision on the imaging characteristics was reached by consensus. Relationships between tumor grade and histological and MRI findings were assessed using statistical analysis.ResultsForty‐four cases met inclusion criteria; 16 patients were PNSTs Grade 1 (low‐grade), 19 were PNSTs Grade 2 (medium‐grade), and 9 were PNSTs Grade 3 (high‐grade). Large volume (P = .03) and severe peripheral contrast enhancement (P = .04) were significantly associated with high tumor grade. Degree of muscle atrophy, heterogeneous signal and tumor growth into the vertebral canal were not associated with grade.Conclusions and Clinical ImportanceGrade of malignancy was difficult to identify based on diagnostic imaging alone. However, some MRI features were predictive of high‐grade PNSTs including tumor size and peripheral contrast enhancement

Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs : a multi‐center randomized parallel group clinical study

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 alpha < .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

Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: A multi-center randomized parallel group clinical study.

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

Neurological abnormalities in 97 dogs with detectable pituitary masses

Background: Pituitary tumours are common neoplasms of the sellar region in small animals. However, detailed information regarding the spectrum and severity of possible neurological signs are lacking. Objective: To retrospectively describe the neurological abnormalities in a population of dogs with a detectable pituitary mass (DPM) and relate them with the size of the mass and magnetic resonance imaging (MRI) signs of brain compression (BC). Client-owned dogs were included in the study if they had MRI showing a DPM and a detailed neurological examination. The neurological signs were evaluated in relation to the pituitary height/brain ratio (P:B ratio) and the presence/absence of brain compression. Results: Ninety-seven dogs were enrolled. Besides abnormal mentation and behaviour (77%), gait (61%) and cranial nerve abnormalities (44%), other unreported neurological signs observed included postural abnormalities (21%), pain and/or hyperesthesia (25%) and abnormal postural and proprioceptive reactions (49%). The majority of dogs with DPM had signs of BC. The presence of a high pituitary height/brain area and BC represented a risk factor for developing mental status abnormalities. Conclusion: Neurological signs recorded in DPM-affected dogs include not only the typical forebrain signs but also gait disturbances and hyperesthesia. Neurological signs are positively associated with increased P:B ratio and MRI signs of brain compression

Studio sulla biopsia tc-guidata del polmone con ago sottile nel cane e nel gatto

La diagnosi delle patologie polmonari sulla base dell’anamnesi e della visita clinica è spesso difficile. La diagnostica per immagini risulta essere di grande importanza in questo settore. La radiologia è stata considerata per molto tempo la tecnica di elezione per lo studio di queste malattie. Tuttavia spesso non è possibile differenziare una lesione infiammatoria/infettiva da una neoplastica. Risulta quindi necessaria una corretta diagnosi cito-istopatologica per avere una diagnosi accurata, una corretta prognosi ed un preciso piano terapeutico. In medicina umana la TC e la biopsia TC-guidata sono indicate in presenza di lesioni non adeguatamente visualizzate con altre procedure diagnostiche. Nel presente studio sono stati sottoposti a biopsia TC-guidata con ago sottile 30 cani e 9 gatti, di differente sesso, razza e dimensioni. In tutti gli animali sono stati eseguiti esame clinico, esami ematici e le radiografie del torace. Nel presente studio 32 campioni su 39 sono risultati diagnostici. Gli altri 7 casi o a causa di incertezza diagnostica, od in quanto contenevano solo sangue sono stati considerati non diagnostici. Non si sono riscontrate complicazioni gravi, solamente 5 casi di lieve pneumotorace.Diagnosis of pulmonary lesions on the basis of history and physical examination is often challenging. Diagnostic imaging is therefore of paramount importance in this field. Radiology has traditionally been considered the elective diagnostic procedure for these diseases. Nonetheless it is often not possible to differentiate inflammatory/infectious lesions from neoplastic disease. A correct cyto-histopathologic diagnosis is therefore needed for an accurate diagnosis and subsequent prognostic and therapeutic plan. In human medicine TC and TC-guided biopsy are indicated in the presence of lesions which are not adequately imaged with other diagnostic procedures. In the present study 30 dogs and 9 cats of different sex, breed and size underwent TCguided lung fine-needle aspiration. Clinical examination, haematology and chest radiography were performed on all animals. In this study 32 samples out of 39 were diagnostic. Other 7 cases either because of uncertainty or only blood was aspirated, were considered non diagnostic. Only mild pneumothorax was seen in 5 cases. No major complications were encountered

SLC19A3 Loss-of-Function Variant in Yorkshire Terriers with Leigh-Like Subacute Necrotizing Encephalopathy

Sporadic occurrence of juvenile-onset necrotizing encephalopathy (SNE) has been previously reported in Yorkshire terriers. However, so far, no causative genetic variant has been found for this breed-specific form of suspected mitochondrial encephalomyopathy. Affected dogs showed gait abnormalities, central visual defects, and/or seizures. Histopathological analysis revealed the presence of major characteristics of human Leigh syndrome and SNE in Alaskan huskies. The aim of this study was to characterize the genetic etiology of SNE-affected purebred Yorkshire terriers. After SNP genotyping and subsequent homozygosity mapping, we identified a single loss-of-function variant by whole-genome sequencing in the canine SLC19A3 gene situated in a 1.7 Mb region of homozygosity on chromosome 25. All ten cases were homozygous carriers of a mutant allele, an indel variant in exon 2, that is predicted to lead to a frameshift and to truncate about 86% of the wild type coding sequence. This study reports a most likely pathogenic variant in SLC19A3 causing a form of SNE in Yorkshire terriers and enables selection against this fatal neurodegenerative recessive disorder. This is the second report of a pathogenic alteration of the SLC19A3 gene in dogs with SNE

Spinal cord neurenteric cyst: clinical and diagnostic findings and long term follow-up in two dogs

open9siNon presenteopenGagliardo, T., Corlazzoli, D., Rosati, M., Specchi, S., Pisoni, L., Del Magno, S., Pappagalli, S., Galli, G., Gandini, G.Gagliardo, T., Corlazzoli, D., Rosati, M., Specchi, S., Pisoni, L., Del Magno, S., Pappagalli, S., Galli, G., Gandini, G