An early clinical phenotype of necrotizing meningoencephalitis in the Pug reveals similarities to multiple sclerosis in humans.

Necrotizing meningoencephalitis (NME) is a fatal neuroinflammatory disease that previously carried a uniformly grave prognosis. Our recent identification of a novel early form of NME in Pugs suggests that disease onset and progression are likely more insidious than previously recognized and provides new hope that early therapeutic intervention may halt disease progression and ultimately prevent or cure NME. This novel perspective also sheds new light on the clinical similarities to multiple sclerosis (MS) in humans and provides a rationale for cross-species translation. The history of recent scientific discoveries in NME and new parallels between MS and NME will be reviewed.

A novel meningioma with tyrosine-rich crystals in a 6-year-old Great Dane.

A 6-year-old female spayed Great Dane was evaluated for acute onset cluster seizures. Magnetic resonance imaging (MRI) identified a mass in the olfactory bulbs with a large mucoid component caudal to the primary mass. The mass was removed via transfrontal craniotomy and histopathology revealed a tyrosine crystalline-rich, fibrous meningioma with a high mitotic index. Repeat MRI at 6 months showed no detectable tumor regrowth. The dog is clinically normal with no seizures at the time of publication 10 months after surgery. This meningioma subtype is rare in humans. This unique meningioma occurred in a dog of younger age and uncommon breed for intracranial meningioma. Biological progression of this tumor subtype is unknown; however, growth rate might be slow despite the high mitotic index.

Brevundimonas vesicularis isolation from a Labrador Retriever with Bacteremia, Endocarditis, Spinal Epidural Empyema, and Polyarthritis.

A 7 yr old spayed female Labrador retriever was evaluated for progressive nonambulatory tetraparesis, obtundation, joint pain, and pyrexia. The dog was diagnosed with spinal epidural empyema, bacteremia, endocarditis, and polyarthritis based on magnetic resonance imaging, echocardiography, joint fluid analysis, and blood culture. Blood culture isolated a rare and atypical pathogen, Brevundimonas vesicularis in conjunction with Escherchia coli. The patient was treated with a 10 mo antibiotic course, and clinical signs quickly resolved. This is the first report of B vesicularis in association with bacteremia, endocarditis, spinal empyema, and polyarthritis in a dog.

Brucella canis discospondylitis in 33 dogs.

Objective: To describe the clinical and imaging findings of 33 dogs with Brucella canis discospondylitis (BDS). Animals: 33 client owned dogs from four veterinary specialty hospitals within Colorado and Arizona with at least one positive B. canis test and spinal diagnostic imaging. Procedures: Retrospective review of signalment, physical and neurological examination findings, laboratory results, B. canis serology, and diagnostic imaging of 33 dogs with BDS. All imaging was reviewed by a board-certified veterinary neurologist. Radiographs were reviewed by a board-certified veterinary radiologist blinded to MRI and CT findings. Results: 31/33 (94%) dogs were <5 years old (median = 2.5 years, mean = 2.9 years, range 0.5-10 years). 21/29 (72%) dogs had signs of nonspecific pain, spinal pain, or lameness for >3 months (median = 6 months, mean = 8.2 months, range 5 days-4 years). Fever was seen in only 4/28 (14%) dogs. Multifocal lesions were evident on radiographs in 21/29 (72%) dogs and MRI in 12/18 (67%) dogs. Smooth, round, central end-plate lysis, defined as "hole punch" lesions, were identified radiographically in 25/29 (86%) dogs. Vertebral physitis or spondylitis without discitis was evident on MRI in 7/18 (39%) dogs. Clinical relevance: Dogs with BDS typically present at a young age with a long duration of clinical signs. Identification of radiographic "hole punch" lesions and MRI evidence of vertebral physitis, spondylitis, and paravertebral inflammation without discitis should increase suspicion for BDS. BDS may be increasing in frequency in the southwestern United States, and dogs with signs of chronic spinal pain and/or lameness should be screened for B. canis.

Diagnosis and Treatment of a Spinal Intraosseous Keratinized Cyst of L1 in a Dog.

An 8 yr old female spayed golden retriever presented for a 3 wk history of progressive pelvic limb ataxia. MRI revealed a well-circumscribed T2-weighted hyperintense, T1-weighted poorly contrast-enhancing extradural mass to the right of the spinal cord at the level of L1 causing severe spinal cord compression. A right-sided hemilaminectomy was performed to remove the mass, and histopathology revealed an intraosseous keratinized cyst. A complete neurologic recovery was made within 2 wk following the surgery. This case illustrates a rare diagnosis and the first case report describing MRI findings and favorable clinical outcome after surgical management of a spinal intraosseous keratinized cyst.

A potential early clinical phenotype of necrotizing meningoencephalitis in genetically at-risk pug dogs.

BACKGROUND: Necrotizing meningoencephalitis (NME) in the pug dogs is a fatal neuroinflammatory disease associated with rapid progression and poor response to conventional immunosuppressive therapy. Diagnosis is typically made after severe neurological abnormalities have manifested. HYPOTHESIS/OBJECTIVE: Pug dogs at genetic risk for NME might manifest neurological abnormalities before developing pathognomonic clinical signs of NME. ANIMALS: Thirty-six pug dogs less than 4 years of age asymptomatic for NME. METHODS: Prospective observational cohort study with germline genome-wide genotyping. Neurological examinations were performed 4 weeks apart to document reproducible findings of central nervous system disease. Magnetic resonance imaging, cerebrospinal fluid analysis, and testing for infectious diseases were performed in all pugs with reproducible abnormalities detected on neurological examination. RESULTS: The overall risk allele frequency in this cohort was 40%; 5 (14%) dogs were high risk, 19 (53%) dogs were medium risk, and 12 (33%) dogs were low genetic risk for NME. Reproducible abnormalities detected on neurological examination were identified in 8/24 (33%) genetically at-risk dogs and 0/12 (0%) low risk dogs. Clinical abnormalities included multifocal spinal pain in 8/8, reduced menace response in 5/8, and lateralizing postural reaction deficits in 5/8 pugs. There was a strong association between genotype risk and the presence of this clinical phenotype (P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Our findings suggest the presence of a novel early clinical phenotype of NME in apparently asymptomatic genetically at-risk pugs which might be used to plan early diagnostic and therapeutic clinical trials.

Prevalence and clinical features of thoracolumbar intervertebral disc-associated epidural hemorrhage in dogs.

BACKGROUND: Intervertebral disc-associated epidural hemorrhage (EH) in dogs is a poorly understood neurological condition. OBJECTIVE: To compare the clinical presentation, magnetic resonance imaging (MRI) changes, and clinical outcome of dogs with acute thoracolumbar intervertebral disc herniation (TL-IVDH) with and without EH. ANIMALS: One hundred sixty client-owned dogs that underwent MRI and hemilaminectomy for acute TL-IVDH at a private practice in Colorado, including 63 dogs with EH and 97 dogs without EH. METHODS: Retrospective review of medical record data from 160 dogs presenting sequentially to a single practice with acute TL-IVDH that underwent MRI and hemilaminectomy surgery. RESULTS: Sixty-three of 160 (39%) dogs had confirmed EH. French Bulldogs were significantly overrepresented (23/63; odds ratio [OR]: 4.1; 95% confidence interval [CI]: 1.8-9.0; P < .001) of the EH cases. Dogs with EH were more likely to present with clinical signs less than 48 hours than were dogs without EH (24-48 vs 48-72 hours; OR: 2.4; 95% CI: 1.2-4.6; P = .02) and were more likely to be nonambulatory on presentation (OR: 2.1; 95% CI: 1.0-4.1; P = .04). Dogs with EH were more likely to have <50% cross-sectional spinal cord compression than dogs without EH (OR: 2.3 vs. 0.4; 95% CI: 1.2-4.4 and 0.2-0.9, respectively), longer longitudinal spinal cord compression (3 spaces vs 1 space, P < .001), and greater intrinsic spinal cord change (grade 3/severe vs grade 1/mild; P < .001) based on MRI. The location of the intervertebral disc herniation in French Bulldogs with EH was more likely to be thoracolumbar (OR: 10.8; 95% CI: 2.1-55.7; P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: French Bulldogs have a high prevalence of intervertebral disc-associated EH. Dogs with EH have a shorter clinical course and are more likely to be nonambulatory on initial presentation.

Corpectomy and spinal stabilization using a 3D-printed spine model and custom jigs to address severe spinal deformities from T9-11 and L2-4 in a 6-month-old German shepherd puppy.

This report describes surgical decompression and stabilization of 2 hemivertebrae in a German shepherd dog. Long-term clinical and imaging outcomes are documented. Spinal cord decompression via corpectomy improved neurological function and intrinsic spinal cord changes on MRI. The dog improved to have minimal paraparesis and an active lifestyle.

Leukocyte and cytokine variables in asymptomatic Pugs at genetic risk of necrotizing meningoencephalitis.

BACKGROUND: Necrotizing meningoencephalitis (NME, aka Pug dog encephalitis) is an inflammatory brain condition associated with advanced disease at initial presentation, rapid progression, and poor response to conventional immunomodulatory therapy. HYPOTHESIS/OBJECTIVES: That genetic risk for NME, defined by a common germline DNA haplotype located on chromosome 12, is associated with altered blood cytokine concentrations and leukocyte subsets in asymptomatic Pugs. ANIMALS: Forty Pug dogs asymptomatic for NME from a hospital sample. METHODS: Prospective observational cohort study, including germline genome-wide genotyping, plasma cytokine determination by multiplexed profiling, and leukocyte subset characterization by flow cytometric analysis. RESULTS: Seven (18%) dogs were high risk, 10 (25%) medium risk, and 23 (58%) low risk for NME, giving a risk haplotype frequency of 30%. High and medium risk Pugs had significantly lower proportion of CD4+ T cells (median 22% [range, 7.3%-38%] vs 29% [range, 16%-41%], P = .03) and higher plasma IL-10 concentrations than low-risk Pugs (median 14.11 pg/mL [range, 9.66-344.19 pg/mL] vs 12.21 pg/mL [range, 2.59-18.53 pg/mL], P = .001). No other variables were significantly associated with the NME haplotype-based risk. CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest an immunological underpinning to NME and a biologic rationale for future clinical trials that investigate novel diagnostic, preventative, and therapeutic strategies for this disease.

Congenital portosystemic shunts in five mature dogs with neurological signs.

Congenital portosystemic shunts are a common cause of hepatic encephalopathy and are typically first identified when dogs are <2 years of age. This case series describes five dogs with congenital portosystemic shunts; the dogs were presented for severe encephalopathic signs during middle or old age. Three dogs had portoazygos shunts, and four dogs had multifocal and lateralizing neurological abnormalities, including severe gait abnormalities and vestibular signs. All five dogs responded to medical or surgical treatment, demonstrating that older animals can respond to treatment even after exhibiting severe neurological signs.

Canine chronic inflammatory rhinitis.

Chronic inflammatory rhinitis is commonly found in dogs with chronic nasal disease and is characterized by lymphoplasmacytic infiltrates in the nasal mucosa in the absence of an obvious etiologic process. The pathogenesis of lymphoplasmacytic rhinitis remains unknown. Animals respond poorly to antibiotics, oral glucocorticoids, and antihistamines, making primary infectious, immune-mediated, or allergic etiologies unlikely. Aberrant immune response to inhaled organisms or allergens may induce inflammation in some animals. Common clinical signs include nasal discharge, sneezing, coughing, epistaxis, and stertor. Diagnosis is made by performing a thorough history, physical examination, radiography or advanced imaging (via computed tomography or magnetic resonance imaging), rhinoscopy, and nasal mucosal biopsy to rule out primary etiologies of nasal discharge. Treatment strategies have included various antibiotics, antihistamines, oral and inhalant steroids, nonsteroidal antiinflammatories, and antifungal medications. Some dogs may respond partially to doxycycline or azithromycin, although it is unclear whether response is related to antimicrobial or antiinflammatory properties of these drugs. Hydration of the nasal cavity through nasal drops or aerosols may limit nasal discharge, and some animals may improve with inhalant (but rarely oral) glucocorticoids.

Molecular detection of microbes in nasal tissue of dogs with idiopathic lymphoplasmacytic rhinitis.

Lymphoplasmacytic rhinitis (LPR) is a common histologic finding in dogs with chronic nasal disease; however, potential etiologies of this disorder have not been examined. We investigated the hypothesis that specific microbes contribute to clinical disease in dogs with LPR. Paraffin-embedded nasal biopsies were obtained from 19 dogs with LPR, 10 dogs with nasal neoplasia, and 10 dogs with nasal aspergillosis. Nucleic acids were extracted from paraffin blocks, and real-time quantitative polymerase chain reaction (PCR) was employed for detection of target genes for bacterial and fungal DNA, canine adenovirus 2 (CAV-2), parainfluenza virus 3 (PI-3), Chlamydial Chlamydophila spp., and Bartonella spp. Conventional PCR was used for detection of Mycoplasma spp. Statistical analysis was performed using the Mann-Whitney U-test for nonparametric data, and significance was set at P < 0.05. DNA or RNA for CAV-2, PI-3, Bartonella, Mycoplasma, and Chlamydophila was not detected in any nasal biopsy. DNA loads for bacterial DNA did not differ among disease groups. Detection of fungal DNA in nasal biopsies was highest in dogs with aspergillosis (P < 0.0001); however, nasal biopsies of LPR dogs also displayed higher fungal DNA levels than samples from dogs with nasal neoplasia (P = 0.016). Detection of high levels of fungal DNA in nasal biopsies of dogs with LPR suggests that fungal organisms may be causally associated with the inflammation observed, although the possibility of entrapment or accumulation of fungi in the nasal cavity due to chronic inflammation cannot be excluded. Further investigations are required to elucidate the underlying etiopathogenesis of LPR.

Idiopathic lymphoplasmacytic rhinitis in dogs: 37 cases (1997-2002).

OBJECTIVE: To determine clinical signs and rhinoscopic, computed tomographic, and histologic abnormalities in dogs with idiopathic lymphoplasmacytic rhinitis. DESIGN: Retrospective case series. ANIMALS: 37 dogs. PROCEDURE: Clinical information was obtained from medical records. Nasal computed tomographic images and histologic slides of biopsy specimens were reviewed. RESULTS: Dogs ranged from 1.5 to 14 years old (mean, 8 years); most (28) were large-breed dogs. Nasal discharge was unilateral in 11 of 26 (42%) dogs and bilateral in 15 of 26 (58%) dogs. In dogs with unilateral disease, duration of clinical signs ranged from 1.5 to 36 months (mean, 8.25 months; median, 2 months), and in dogs with bilateral disease, duration of signs ranged from 1.25 to 30 months (mean, 6.5 months; median, 4 months). Computed tomography (n = 33) most often revealed fluid accumulation (27/33 [82%]), turbinate destruction (23/33 [70%]), and frontal sinus opacification (14/33 [42%]). Rhinoscopy (n = 37) commonly demonstrated increased mucus and epithelial inflammation; turbinate destruction was detected in 8 of 37 (22%) dogs. Bilateral biopsy specimens from all 37 dogs were examined. Four dogs had only unilateral inflammatory changes. The remaining 33 dogs had bilateral lesions; in 20, lesions were more severe on 1 side than the other. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggest that idiopathic lymphoplasmacytic rhinitis is a key contributor to chronic nasal disease in dogs and may be more common than previously believed. In addition, findings suggest that idiopathic lymphoplasmacytic rhinitis is most often a bilateral disease, even among dogs with unilateral nasal discharge.