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.

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.

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.

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.