Prevalence of thoracic vertebral malformations in french bulldogs, pugs and english bulldogs with and without associated neurological deficits

Congenital vertebral malformations are common incidental findings in small breed dogs. This retrospective observational study evaluated the type and prevalence of thoracic vertebral malformations in 171 neurologically normal and 10 neurologically abnormal screw-tailed brachycephalic dogs. Neurologically normal dogs underwent CT for reasons unrelated to spinal disease, while affected dogs underwent MRI. Imaging studies were reviewed and vertebral malformations including hemivertebrae, block vertebrae, transitional vertebrae, and spina bifida were documented. The group of clinically normal dogs consisted of 62 French bulldogs, 68 Pugs and 41 English bulldogs. The group of affected dogs consisted of one French bulldog and nine Pugs. Overall, 80.7% of neurologically normal animals were affected by at least one vertebral malformation. There was a significant influence of breed, with thoracic vertebral malformations occurring more often in neurologically normal French bulldogs (P < 0.0001) and English bulldogs (P = 0.002). Compared to other breeds, hemivertebrae occurred more often in neurologically normal French bulldogs (93.5%; P < 0.0001 vs. Pugs; P = 0.004 vs. English bulldogs) and less often in neurologically normal Pugs (17.6%; P = 0.004 vs. English bulldogs). Neurologically normal Pugs were more often diagnosed with transitional vertebrae and spina bifida compared to other breeds (P < 0.0001 for both malformations). Of Pugs included in the study, 4.7% were diagnosed with clinically relevant thoracic vertebral malformations. When compared to the general veterinary hospital population, this was significantly more than the other two breeds (P = 0.006). This study indicates that thoracic vertebral malformations occur commonly in neurologically normal screw-tailed brachycephalic dogs. While hemivertebrae are often interpreted as incidental diagnostic findings, they appear to be of greater clinical importance in Pugs compared to other screw-tailed brachycephalic breeds

Evaluation of radiography as a screening method for detection and characterisation of congenital vertebral malformations in dogs

Congenital vertebral malformations (CVM) are common in brachycephalic ‘screw-tailed’ dogs; they can be associated with neurological deficits and a genetic predisposition has been suggested. The purpose of this study was to evaluate radiography as a screening method for congenital thoracic vertebral malformations in brachycephalic ‘screw-tailed’ dogs by comparing it with CT. Forty-nine dogs that had both radiographic and CT evaluations of the thoracic vertebral column were included. Three observers retrospectively reviewed the images independently to detect CVMs. When identified, they were classified according to a previously published radiographic classification scheme. A CT consensus was then reached. All observers identified significantly more affected vertebrae when evaluating orthogonal radiographic views compared with lateral views alone; and more affected vertebrae with the CT consensus compared with orthogonal radiographic views. Given the high number of CVMs per dog, the number of dogs classified as being CVM free was not significantly different between CT and radiography. Significantly more midline closure defects were also identified with CT compared with radiography. Malformations classified as symmetrical or ventral hypoplasias on radiography were frequently classified as ventral and medial aplasias on CT images. Our results support that CT is better than radiography for the classification of CVMs and this will be important when further evidence of which are the most clinically relevant CVMs is identified. These findings are of particular importance for designing screening schemes of CVMs that could help selective breeding programmes based on phenotype and future studies

An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed

Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genotyping of additional cases and controls and RNAseq analysis provided strong evidence that the inversion is causal. Evidence of cryptic splicing resulting in novel exon transcription for FAM134B was identified by RNAseq experiments. This investigation demonstrates the identification of a novel sensory neuropathy associated mutation, by mapping using a minimal set of cases and subsequent genome sequencing. Through mutation screening, it should be possible to reduce the frequency of or completely eliminate this debilitating condition from the Border Collie breed population

Clinical findings and outcome of dogs with unilateral masticatory muscle atrophy

Background: Little is known about the spectrum of underlying disorders in dogs with unilateral masticatory muscle (MM) atrophy. Objectives: To evaluate the clinical presentation, magnetic resonance imaging (MRI) findings, and outcome of dogs with unilateral MM atrophy. Animals: Sixty‐three client‐owned dogs. Methods: The medical database was retrospectively reviewed for dogs that underwent MRI for evaluation of unilateral MM atrophy. Imaging studies were reviewed and follow‐up information was obtained from telephone interviews. Results: Presumptive trigeminal nerve sheath tumor (pTNST) was diagnosed in 30 dogs (47.6%); survival time varied from 1 day to 21 months (median, 5 months). Other extra‐axial mass lesions were observed in 13 dogs (20.6%); survival time varied from 6 days to 25 months (median, 2.5 months). In 18 dogs (28.6%), no abnormalities were observed on MRI; neurological signs only progressed in 1 dog. Diagnosis had a significant influence on the type of neurological abnormalities, with additional neurological deficits observed in most dogs with pTNST and in all dogs with other extra‐axial mass lesions. Diagnosis had a significant effect on euthanasia at the time of diagnosis and likelihood of neurological deterioration. Dogs with mass lesions were more likely to be euthanized or experience neurological deterioration, whereas these outcomes occurred less often in dogs in which no causative lesion could be identified. Conclusions and Clinical Importance: Trigeminal nerve sheath tumors should not be considered the only cause of unilateral MM atrophy. Our results illustrate the importance of performing a neurological examination and MRI when evaluating dogs with unilateral MM atrophy

The occurrence of cardiac abnormalities in canine steroid‐responsive meningitis arteritis

Objectives: To document the prevalence of cardiac abnormalities in dogs with steroid‐responsive meningitis arteritis and to assess resolution of these abnormalities following corticosteroid therapy. Materials and Methods: Steroid‐responsive meningitis arteritis was diagnosed based on signalment, physical examination findings, complete blood count, biochemistry and CSF analysis. Echocardiography, C‐reactive protein and cardiac troponin I were measured in all cases before and 10 to 14 days after commencing corticosteroid therapy. Fibrinogen was also measured in a proportion of dogs. Results: Fourteen dogs were prospectively enrolled. Increased cardiac troponin I was identified in five of 14 dogs and echocardiographic abnormalities were detected in 12 of 14 dogs, including spontaneous echo contrast (12 of 14), mild pericardial effusion (five of 14) and mildly decreased fractional shortening (five of 14). All dogs had increased C‐reactive protein and fibrinogen was increased in 11 of 12. Corticosteroid treatment was associated with clinical improvement and normalisation of C‐reactive protein in all dogs. The cardiac troponin I levels normalised in four of five and fibrinogen had normalised in all five dogs which were retested. Spontaneous echo contrast improved or completely resolved in 12 of 12 and pericardial effusion resolved in five of five dogs. Fractional shortening normalised in two of five dogs. Clinical Significance: Cardiac changes are common in dogs with steroid‐responsive meningitis arteritis and most resolve with therapy. Further investigation into the cause and significance of these changes is necessary in determining whether antithrombotic therapy or positive inotropic therapy is indicated

Comparison of signalment and computed tomography findings in French Bulldogs, Pugs, and English Bulldogs with and without clinical signs associated with thoracic hemivertebra

Background: Although thoracic hemivertebra can cause neurological signs, they occur commonly in neurologically normal dogs. Objectives: To evaluate whether computed tomography (CT) findings and factors associated with signalment can be used to differentiate between dogs with and without neurological signs associated with hemivertebra. Animals: One hundred sixty dogs with ≥1 hemivertebrae were retrospectively studied. This group consisted of 40 dogs with clinical signs caused by hemivertebra and 40 French Bulldogs, 40 Pugs, and 40 English Bulldogs that underwent CT for reasons unrelated to neurological disease. Methods: All dogs underwent CT and affected dogs also underwent magnetic resonance imaging. All CT studies were randomly evaluated by an observer blinded to signalment and clinical status. The following variables were evaluated: presence, number, location, and subtype of hemivertebra; presence of vertebral subluxation; severity of vertebral canal stenosis; presence, location, and severity of kyphosis, and number of vertebrae involved in the kyphotic segment. Statistical modeling was performed to identify factors associated with clinical status. Results: Pug breed (odds ration [OR], 10.8; P = .01), more severe kyphosis (OR, 1.1 per grade increase; P < .001), fewer instead of more observed hemivertebrae (OR, 0.8; P = 0.03), and ventrolateral hypoplasia hemivertebra subtype (OR, 4.0; P = .011) were associated with higher likelihood of neurological disease. A Cobb angle of 34.5 degrees corresponded with the highest combined sensitivity and specificity to differentiate between clinically affected and unaffected dogs. Conclusions and Clinical Importance: The variables identified could aid in differentiating between clinically relevant and irrelevant hemivertebra in small breed brachycephalic dogs

Mitochondrial fission factor (MFF) frameshift variant in Bullmastiffs with mitochondrial fission encephalopathy.

Familial cerebellar ataxia with hydrocephalus in Bullmastiffs was described almost 40 years ago as a monogenic autosomal recessive trait. We investigated two young Bullmastiffs showing similar clinical signs. They developed progressive gait and behavioural abnormalities with an onset at around 6 months of age. Neurological assessment was consistent with a multifocal brain disease. Magnetic resonance imaging of the brain showed intra-axial bilateral symmetrical focal lesions localised to the cerebellar nuclei. Based on the juvenile age, nature of neurological deficits and imaging findings, an inherited disorder of the brain was suspected. We sequenced the genome of one affected Bullmastiff. The data were compared with 782 control genomes of dogs from diverse breeds. This search revealed a private homozygous frameshift variant in the MFF gene in the affected dog, XM_038574000.1:c.471_475delinsCGCTCT, that is predicted to truncate 55% of the wild type MFF open reading frame, XP_038429928.1: p.(Glu158Alafs*14). Human patients with pathogenic MFF variants suffer from 'encephalopathy due to defective mitochondrial and peroxisomal fission 2'. Archived samples from two additional affected Bullmastiffs related to the originally described cases were obtained. Genotypes in a cohort of four affected and 70 unaffected Bullmastiffs showed perfect segregation with the disease phenotype. The available data together with information from previous disease reports allow classification of the investigated MFF frameshift variant as pathogenic and probably causative defect of the observed neurological phenotype. In analogy to the human phenotype, we propose to rename this disease 'mitochondrial fission encephalopathy (MFE)'

Toxicity results after treatment with Electronic Brachytherapy in patients with endometrial cancer

Poster Session [EP-2226] Purpose or Objective To analyse the toxicity outcomes after treatment with Electronic Brachytherapy (XB) in postsurgical endometrial cancer patients treated at our medical centre. Material and Methods Prospective study in which we selected 94 patients, between September/2015 and September/2017, that received treatment with XB administered twice a week after endometrial cancer surgery, with IMRT planificati on. The patients were divided in two groups: Group 1 (57/94) considered high risk received external beam radiotherapy (46Gy) followed by XB (15Gy in 5Gy fractions) and group 2 (37/94) considered intermediate risk received exclusive XB (25Gy in 5Gy fraction s). We analysed the median dose in bladder, rectum and sigmoid D2cc, V50, V35 with XB comparing the doses with Ir192. The vaginal mucosa, gastrointestinal (GI) and genitourinary (GU) toxicities were analysed with the Common Terminology Criteria for Adverse Events (CTCAE 4.0) scale. Results The median dose in bladder with XB vs. Ir192 was: 2cc 62.9 vs. 69.9%, V50 7.1 vs. 12.6Gy, V35 15 vs. 28.1. In rectum XB vs. Ir192 was: D 2cc 64.01% vs. 67.7%, V50 7.8 vs. 10.9Gy, V35 16.5 vs. 31.8Gy. In sigmoid XB vs. Ir 192 was: D 50.37%vs. 58.0%, V50 8.8 vs. 16.2Gy, V35 21.2 vs. 37.5Gy. The median follow- up was 11 months (range 1 - 23, 9 months). In group 1, acute vaginal mucositis (G1) was observed in 35.08% of the patients, GI toxicity (G1) in 5.26% and GU toxicity (G1) in 10.52%. In group 2, we observed acute vaginal mucositis G1 in 45% of the patients and G2 in 10.81%, GI toxicity (G1) occurred in 2.7% and GU toxicity (G1) was present in 16.21%. There was no grade 3 or greater toxicity in any of the groups. Late toxici ty was observed in only 4 patients: Mucositis (G1) in 3 patients and GU toxicity (G1) in 1 patient. Conclusion The dose received by the organs at risk with the XB is less compared to Ir192, with a good coverage of the PTV. The greater toxicity was observe d immediately after the treatment was finished with an important reduction of the symptoms after 6 months. This technique shows excellent results as for toxicity

Evaluation of the influence of kyphosis and scoliosis on intervertebral disc extrusion in French bulldogs

Although thoracic vertebral malformations with kyphosis and scoliosis are often considered incidental findings on diagnostic imaging studies of screw-tailed brachycephalic breeds, they have been suggested to interfere with spinal biomechanics and intervertebral disc degeneration. It is however unknown if an abnormal spinal curvature also predisposes dogs to develop clinically relevant intervertebral disc herniations. The aim of this study was to evaluate if the occurrence of thoracic vertebral malformations, kyphosis or scoliosis would be associated with a higher prevalence of cervical or thoracolumbar intervertebral disc extrusion in French bulldogs

Clinical Features, Imaging Characteristics, and Long-term Outcome of Dogs with Cranial Meningocele or Meningoencephalocele

BACKGROUND: The term meningoencephalocele (MEC) describes a herniation of cerebral tissue and meninges through a defect in the cranium, whereas a meningocele (MC) is a herniation of the meninges alone.HYPOTHESIS/OBJECTIVES: To describe the clinical features, magnetic resonance imaging (MRI) characteristics, and outcomes of dogs with cranial MC and MEC.ANIMALS: Twenty-two client-owned dogs diagnosed with cranial MC or MEC.METHODS: Multicentric retrospective descriptive study. Clinical records of 13 institutions were reviewed. Signalment, clinical history, neurologic findings and MRI characteristics as well as treatment and outcome were recorded and evaluated.RESULTS: Most affected dogs were presented at a young age (median, 6.5 months; range, 1 month - 8 years). The most common presenting complaints were seizures and behavioral abnormalities. Intranasal MEC was more common than parietal MC. Magnetic resonance imaging identified meningeal enhancement of the protruded tissue in 77% of the cases. Porencephaly was seen in all cases with parietal MC. Cerebrospinal fluid (CSF) analysis identified mild abnormalities in 4 of 11 cases. Surgery was not performed in any affected dog. Seventeen patients were treated medically, and seizures were adequately controlled with anti-epileptic drugs in 10 dogs. Dogs with intranasal MEC and mild neurologic signs had a fair prognosis with medical treatment.CONCLUSION AND CLINICAL IMPORTANCE: Although uncommon, MC and MEC should be considered as a differential diagnosis in young dogs presenting with seizures or alterations in behavior. Medical treatment is a valid option with a fair prognosis when the neurologic signs are mild.</p