Novel COL6A3 frameshift variant in American Staffordshire Terrier dogs with Ullrich-like congenital muscular dystrophy.

Two (male and female) 10-month-old American Staffordshire Terrier littermates presented for progressive weakness, joint contracture, and distal limb joint hyperlaxity beginning around 6 months of age. Neurological examination, serum creatine kinase activity, infectious disease titers, cerebrospinal fluid analysis, and electrodiagnostic testing were performed. Muscle biopsies were collected for histopathology and immunofluorescence staining for localization of dystrophy associated proteins. Whole-genome sequencing (WGS) was performed on 1 affected dog. Variants were compared to a database of 671 unaffected dogs of multiple breeds. Histopathology confirmed a dystrophic phenotype and immunofluorescence staining of muscle cryosections revealed an absence of staining for collagen-6. WGS identified a homozygous 1 bp deletion in the COL6A3 gene, unique to the first affected dog. Sanger sequencing confirmed the homozygous presence of the frameshift variant in both affected dogs. This report describes the clinical features and most likely genetic basis of an Ullrich-like recessively inherited form of congenital muscular dystrophy in American Staffordshire Terriers.

Successful resuscitation and neurological monitoring of a dog with out-of-hospital cardiopulmonary arrest due to pentobarbital overdose.

OBJECTIVE: To describe the clinical signs, electroencephalographic (EEG) findings, treatment, and outcome in a dog after successful resuscitation from out-of-hospital cardiopulmonary arrest (OHCA) induced by pentobarbital intoxication. CASE SUMMARY: A 10-year-old, male intact Jack Russell Terrier was referred for management of refractory status epilepticus and presented dead on arrival. After 7 minutes of cardiopulmonary resuscitation, return of spontaneous circulation was achieved, but the dog remained comatose, apneic, and lacked brainstem reflexes on neurological examination 6 hours following resuscitation. Magnetic resonance imaging showed polioencephalomalacia consistent with prolonged epileptiform activity, and EEG was initially concerning for electrocerebral inactivity. Following supportive care that included short-term mechanical ventilation, the dog made a full recovery and was discharged from the hospital alive 7 days postresuscitation. It was later revealed that the dog had been administered an unknown amount of pentobarbital during transportation, which likely contributed to the OHCA, clinical, and EEG findings. NEW INFORMATION PROVIDED: This is the first report to describe the full recovery and hospital discharge of a dog suffering OHCA and the first description of EEG findings in a clinical veterinary patient following cardiopulmonary arrest and successful resuscitation. Factors likely contributing to successful patient outcome and potential benefits and limitations of EEG in monitoring postcardiac arrest patients are discussed.

Horner syndrome as a physiological biomarker of disease in canine cervical myelopathy.

BACKGROUND: Horner syndrome often occurs with cervical myelopathies and might provide insight into the underlying disease and prognosis. OBJECTIVES: To describe the clinical and imaging features of dogs with cervical myelopathy and concurrent Horner syndrome and to determine association of Horner syndrome with diseases or magnetic resonance images (MRI). ANIMALS: Ninety-three client-owned dogs with cervical myelopathy and concurrent Horner syndrome and 99 randomly selected client-owned dogs with cervical myelopathy without Horner syndrome (control cases). METHODS: Retrospective study. Medical records were reviewed to identify Horner and control cases and clinical findings recorded. MRI were reviewed, and lesions characterized and recorded. Descriptive and comparative statistics were performed. RESULTS: Non-compressive disease occurred more frequently in the Horner group compared with controls (58%; 95% CI: 48-68 vs 9%; 95% CI: 5-16; P < .0001). The most common diseases were fibrocartilaginous embolism in the Horner group (44/93; 47%) and intervertebral disc extrusion (76/99; 77%) amongst controls. On MRI, parenchymal hyperintensity was seen more commonly in the Horner group (95%; 95% CI: 88-98) compared with controls (51%; 95% CI: 41-60; P < .0001). In the Horner group, dogs that did not survive to discharge (N = 13) had more extensive MRI lesions relative to the adjacent vertebral length (200%; IQR 110%-575%) compared with survivors (N = 80; 110%; IQR 40%-250%; P = .02). Lateralization of Horner signs and MRI changes matched in 54% of cases. The overall survival rate was high in both Horner (80/93; 86%) and control (95/99; 96%) groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Horner syndrome in cervical myelopathy is commonly associated with noncompressive intraparenchymal disease.

Perception of challenges in management of neurological cases in the emergency room.

OBJECTIVE: To investigate emergency clinicians' comfort level in assessing neurological emergencies and to identify opportunities to foster enhanced training of clinical neurology in the emergency room. DESIGN: Internet-based survey. SETTING: University teaching hospitals and private referral centers. SUBJECTS: One hundred and ninety-two emergency and critical care specialists and resident trainees (ECC) and 104 neurology specialists and resident trainees (NEUR) in clinical practice. INTERVENTIONS: An internet-based survey was distributed via veterinary professional organizations' listserves and message boards and responses were collected between March and April 2020. ECC completed a survey evaluating stress levels associated with neurological emergencies, confidence with neurological examinations, and neuroanatomical localization. NEUR completed a similar survey to report their perception of their ECC colleagues' confidence in the assessment of neurological cases. Chi-square and Mann-Whitney U-tests were used to compare categorical responses and confidence scores between groups. P < 0.002 was considered significant. MEASUREMENTS AND MAIN RESULTS: Fifty-two percent of ECC found neurological emergencies slightly challenging, whereas 85% of NEUR found them moderately to extremely challenging for ECC (P < 0.0001). ECC's median self-reported confidence score in performing a neurologic examination on a scale of 0-100 was 75 (interquartile range [IQR], 27), while NEUR reported a median ECC confidence of 44 (IQR, 25; P < 0.0001). Median self-reported ECC confidence in localizing intracranial, spinal, and neuromuscular disease was 67 (IQR, 40), 88 (IQR, 21), and 60 (IQR, 37), respectively, which was significantly higher than median NEUR-reported ECC confidence of 35 (IQR, 38), 51 (IQR, 31), and 18 (IQR, 20), respectively (all P < 0.0001). Following case transfer, 34% of ECC received NEUR feedback in >75% of cases. CONCLUSIONS: Noticeable discrepancies between ECC and NEUR perceptions of ECC clinical confidence were seen, while no firm evidence of neurophobia could be inferred. Improvements in interdepartmental communication and teaching of clinical neurology may be warranted.

MRI and CT characteristics of a grade I meningioma with concurrent cribriform plate lysis in a dog.

A 6-year-old female spayed German Shepherd mixed-breed dog was presented for treatment of a frontal lobe mass diagnosed on MRI, after an acute onset of generalized seizures and behavior changes. Computed tomography of the head was performed for radiation therapy planning and revealed concurrent cribriform plate lysis without nasal sinus invasion, and focal lysis of the left ventrolateral cranial fossa. Histopathology of the mass obtained via surgical excision was consistent with a grade I fibrous meningioma. The dog had a good outcome following surgery and radiation therapy.

Case Report: MRI, Clinical, and Pathological Correlates of Bromethalin Toxicosis in Three Dogs.

Bromethalin toxicosis is an increasingly common clinical presentation in dogs that may be fatal depending on the extent of intoxication. Antemortem diagnosis of bromethalin toxicosis was achieved in three dogs by demonstration of the active metabolite desmethylbromethalin in fat or serum. Magnetic resonance imaging (MRI) findings were consistent with a diffuse leukoencephalopathy with restricted diffusion and prominent involvement of the corticospinal motor tracts on T2-weighted and diffusion-weighted sequences. Imaging findings were confirmed in one non-surviving dog at necropsy. Resolution of MRI abnormalities was demonstrated in one surviving dog that was consistent with the associated resolution of clinical signs. Initial findings in these dogs support further investigation of specific MRI patterns in cases of leukoencephalopathy to aid differential diagnosis. While antemortem detection of bromethalin and its metabolites confirms exposure, quantitation may be informative as a prognostic biomarker.

Neurological examination in healthy adult inland bearded dragons (Pogona vitticeps).

OBJECTIVE: To evaluate neurological tests and expected results in inland bearded dragons (Pogona vitticeps) and generate recommendations for bearded dragon-specific neurological examination. ANIMALS: 26 healthy adult inland bearded dragons. PROCEDURES: A complete neurological examination utilizing tests described in both mammals and reptiles was performed on each lizard, and test feasibility and outcome were recorded. RESULTS: Tests with poor feasibility included oculocardiac reflex (successfully completed in 62% [16/26] of animals) and voluntary ambulation and swallowing by use of a food item (0% [0/26] of animals). Tests with outcomes considered abnormal in mammals but attributable to normal bearded dragon behavior included head position (head tilt present in 12% [3/26]) and head movement (head bob present in 4% [1/26]). Many tests had absent or inconsistent outcomes, including menace response (present in 19% [5/26]), proprioceptive positioning (present in 4% [1/26] in the thoracic limbs and 0% [0/26] in the pelvic limbs), vent reflex (present in 27% [7/26]), and myotatic reflexes (biceps present in 8% [2/26]; patellar, gastrocnemius, and triceps present in 0% [0/26]). Extensor postural thrust was absent in all successfully tested animals, but a novel reflex termed the caudal thoracic extensor reflex was noted instead in all observed animals (100% [21/21]). CLINICAL RELEVANCE: Tests with poor feasibility or inconsistent outcomes should have low priority or be excluded from neurological examinations of inland bearded dragons. Normal behaviors should be considered for head position and movement. A bearded dragon-specific neurological examination protocol derived from these findings is described and recommended in order to decrease stress and improve neurolocalization.

Serum phosphorylated neurofilament heavy chain as a diagnostic biomarker for progressive myelomalacia in dogs with thoracolumbar intervertebral disc herniation.

BACKGROUND: Serum phosphorylated neurofilament-heavy chain (pNF-H) has not been longitudinally evaluated in dogs that develop progressive myelomalacia (PMM) after Type I intervertebral disc herniation (IVDH). OBJECTIVES: To determine if serum pNF-H concentrations would predict outcome of neuroligical disease in dogs with acute, severe thoracolumbar myelopathy secondary to Type I IVDH. ANIMALS: Thirty-nine client-owned dogs with thoracolumbar myelopathy secondary to IVDH. METHODS: Prospective controlled cohort study. Serum was collected from dogs undergoing hemilaminectomy at multiple timepoints. Final neurological status was established at 12 months and groups were stratified accordingly. Comparisons between outcome and pNF-H concentration at each timepoint was examined using Kruskal-Wallis analysis of variance on ranks and receiver operator characteristics curve analysis. RESULTS: Median serum pNF-H concentrations were not significantly different between deep pain negative dogs that did or did not recover at any timepoint (baseline: 0.37 ng/mL [0-0.9 ng/mL] vs 0 ng/mL [0-0.9 ng/mL], P > 1; 24 hours: 1.25 ng/mL [0.35-7.23 ng/mL] vs 1.53 ng/mL [0-11.94 ng/mL], P > 1; 48 hours: 1.22 ng/mL [0.63-6.62 ng/mL] vs 2.12 ng/mL [0-20.72 ng/mL], P > 1; 72 hours: 2.77 ng/mL [1.33-6.62 ng/mL] vs 16.69 ng/mL [4.02-40.12 ng/mL], P > 1). Dogs that developed PMM had significantly higher serum pNF-H concentrations after surgery compared to all other cohorts at 24 hours: 39.88 ng/mL (25.74-50.68 ng/mL); P < .05 and 72 hours: 223.9 ng/mL (155.4-263.7 ng/mL); P < .05. A serum pNF-H concentration ≥31.39 ng/mL was 83.33% sensitive and 100% specific for identifying PMM in this cohort. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum pNF-H is a promising biomarker for antemortem diagnosis of PMM in dogs with acute, severe thoracolumbar myelopathy secondary to Type I IVDH.

Glioma-associated microglia/macrophages augment tumorigenicity in canine astrocytoma, a naturally occurring model of human glioma.

BACKGROUND: Glioma-associated microglia/macrophages (GAMs) markedly influence glioma progression. Under the influence of transforming growth factor beta (TGFB), GAMs are polarized toward a tumor-supportive phenotype. However, neither therapeutic targeting of GAM recruitment nor TGFB signaling demonstrated efficacy in glioma patients despite efficacy in preclinical models, underscoring the need for a comprehensive understanding of the TGFB/GAM axis. Spontaneously occurring canine gliomas share many features with human glioma and provide a complementary translational animal model for further study. Given the importance of GAM and TGFB in human glioma, the aims of this study were to further define the GAM-associated molecular profile and the relevance of TGFB signaling in canine glioma that may serve as the basis for future translational studies. METHODS: GAM morphometry, levels of GAM-associated molecules, and the canonical TGFB signaling axis were compared in archived samples of canine astrocytomas versus normal canine brain. Furthermore, the effect of TGFB on the malignant phenotype of canine astrocytoma cells was evaluated. RESULTS: GAMs diffusely infiltrated canine astrocytomas. GAM density was increased in high-grade tumors that correlated with a pro-tumorigenic molecular signature and upregulation of the canonical TGFB signaling axis. Moreover, TGFB1 enhanced the migration of canine astrocytoma cells in vitro. CONCLUSIONS: Canine astrocytomas share a similar GAM-associated immune landscape with human adult glioma. Our data also support a contributing role for TGFB1 signaling in the malignant phenotype of canine astrocytoma. These data further support naturally occurring canine glioma as a valid model for the investigation of GAM-associated therapeutic strategies for human malignant glioma.

Diagnosis and clinical outcome following surgical resection of an intracranial grade III anaplastic gemistocytic astrocytoma in a cat.

CASE SUMMARY: A 10-year-old Maine Coon cat was presented for acute onset seizures and cerebrothalamic signs. An intracranial mass, suspected to be a meningioma, was diagnosed on MRI and surgically excised. Histopathology appeared consistent with an atypical meningioma. However, following rapid regrowth of the neoplasm, the patient was humanely euthanized 3 months later. On post-mortem histopathology, the neoplasm was diagnosed as a grade III anaplastic gemistocytic astrocytoma. RELEVANCE AND NOVEL INFORMATION: Gemistocytic astrocytomas are rare brain tumors in the feline patient. This case represents the first report of a feline grade III anaplastic gemistocytic astrocytoma in the cerebrum of a cat with surgical excision and recurrence. The challenging nature of ante-mortem diagnosis and the guarded prognosis, despite surgical intervention, are presented in this report.

Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis.

Feline infectious peritonitis (FIP) is caused by a mutant biotype of the feline enteric coronavirus. The resulting FIP virus (FIPV) commonly causes central nervous system (CNS) and ocular pathology in cases of noneffusive disease. Over 95% of cats with FIP will succumb to disease in days to months after diagnosis despite a variety of historically used treatments. Recently developed antiviral drugs have shown promise in treatment of nonneurological FIP, but data from neurological FIP cases are limited. Four cases of naturally occurring FIP with CNS involvement were treated with the antiviral nucleoside analogue GS-441524 (5-10 mg/kg) for at least 12 weeks. Cats were monitored serially with physical, neurologic, and ophthalmic examinations. One cat had serial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis (including feline coronavirus [FCoV]) titers and FCoV reverse transcriptase [RT]-PCR) and serial ocular imaging using Fourier-domain optical coherence tomography (FD-OCT) and in vivo confocal microscopy (IVCM). All cats had a positive response to treatment. Three cats are alive off treatment (528, 516, and 354 days after treatment initiation) with normal physical and neurologic examinations. One cat was euthanized 216 days after treatment initiation following relapses after primary and secondary treatment. In 1 case, resolution of disease was defined based on normalization of MRI and CSF findings and resolution of cranial and caudal segment disease with ocular imaging. Treatment with GS-441524 shows clinical efficacy and may result in clearance and long-term resolution of neurological FIP. Dosages required for CNS disease may be higher than those used for nonneurological FIP.

Clinical and magnetic resonance imaging (MRI) findings in 26 dogs with canine osseous-associated cervical spondylomyelopathy.

The potential link between degenerative changes seen on magnetic resonance imaging (MRI) in osseous-associated cervical spondylomyelopathy (OA-CSM) and clinical signs has not been explored. Our goal was to retrospectively evaluate MRI findings, while investigating potential correlations between these changes, signalment, and clinical signs. Twenty-six dogs diagnosed with OA-CSM were included in the study. Clinical signs were converted into a Modified Frankel Score (MFS) and MRI findings were assessed and graded. Giant breeds had multiple compressed sites and presented at a younger age than large breeds, suggesting a different underlying pathophysiology. Spinal cord compression, most commonly bilateral, was present in 36.8% of intervertebral spaces. Synovial fluid loss and articular process sclerosis were the most common degenerative changes. Most dogs showed identical MFS scores, and no significant correlations were found between MFS and MRI changes. More detailed functional scales should be used to investigate this in the future.

Constatations cliniques et résultats de l'imagerie par résonance magnétique (IRM) chez 26 chiens atteints de spondylomyélopathie cervicale osseuse canine. Le lien potentiel entre les changements dégénératifs observés sur l'imagerie par résonance magnétique (IRM) dans la spondylomyélopathie cervicale osseuse (SMC-O) et les signes cliniques n'a pas été exploré. Notre but consistait à évaluer rétrospectivement les résultats de l'IRM, tout en faisant enquête sur les corrélations potentielles entre ces changements, le signalement et les signes cliniques. Vingt-six chiens diagnostiqués avec la SMC-O ont été inclus dans l'étude. Les signes cliniques ont été convertis en une cote Frankel modifiée (CFM) et les résultats de l'IRM ont été évalués et cotés. Les races géantes présentaient des sites de compression multiples et étaient atteintes à un plus jeune âge que les grandes races, ce qui suggère une pathophysiologie sous-jacente différente. La compression de la moelle épinière, le plus souvent bilatérale, était présente dans 36,8 % des espaces intervertébraux. La perte de liquide synovial et la sclérose du processus articulaire constituaient les changements dégénératifs les plus fréquents. Des cotes de CFM identiques ont été signalées chez la plupart des chiens et aucune corrélation significative n'a été constatée entre les changements de la CFM et de l'IRM. Des échelles fonctionnelles plus détaillées devraient être utilisées pour enquêter ces cas dans l'avenir.(Traduit par Isabelle Vallières).