Allele frequency of a genetic risk variant for necrotizing meningoencephalitis in pug dogs from Europe and association with the clinical phenotype.

Introduction: Necrotizing meningoencephalitis (NME) in pugs is a potentially fatal disease, which needs lifelong treatment with immunosuppressive or immunomodulatory drugs and shares parallels with acute fulminating multiple sclerosis. Genetic variants of the DLA class II gene are associated with an increased risk for NME. Genetic testing is recommended prior to breeding. The aim of this study was to describe the current allele frequency of a previously identified NME risk variant in the European pug population. A secondary aim was to investigate the association of the NME risk variant with the clinical phenotype in pugs. Methods: Results of genetic testing for the CFA12:2605517delC variant in European pugs between 2012 and 2020 were retrieved (n = 5,974). A validated questionnaire was mailed to all submitters of samples for further information on neurological signs, diagnostic tests, and disease course. Results: The allele frequency of the CFA12 NME risk variant was 25.7% in the European pug population dogs; 7.4% of the dogs were homozygous and 36.7% were heterozygous for the NME risk variant on CFA12. Completed questionnaires were available in 203 dogs including 25 dogs with epileptic seizures or other neurological signs. The clinical phenotype was consistent with NME in 3.9% with a median age of onset of 1.0 years, and indicative of idiopathic epilepsy in 2.9% with a median onset of 2.5 years. Eleven dogs remained unclassified. Pugs with the NME phenotype were significantly more frequently homozygous for the NME risk variant on CFA12 compared to pugs ≥6 years without neurological signs or seizures (p = 0.008). Discussion: The CFA12:2605517delC genetic risk variant is widely distributed in the European pug population and frequently homozygous in pugs with a NME phenotype. The data support the clinical relevance of the CFA12:2605517delC genetic risk variant.

Clinical features, diagnosis, and survival analysis of dogs with glioma.

BACKGROUND: Gliomas in dogs remain poorly understood. OBJECTIVES: To characterize the clinicopathologic findings, diagnostic imaging features and survival of a large sample of dogs with glioma using the Comparative Brain Tumor Consortium diagnostic classification. ANIMALS: Ninety-one dogs with histopathological diagnosis of glioma. METHODS: Multicentric retrospective case series. Signalment, clinicopathologic findings, diagnostic imaging characteristics, treatment, and outcome were used. Tumors were reclassified according to the new canine glioma diagnostic scheme. RESULTS: No associations were found between clinicopathologic findings or survival and tumor type or grade. However, definitive treatments provided significantly (P = .03) improved median survival time (84 days; 95% confidence interval [CI], 45-190) compared to palliative treatment (26 days; 95% CI, 11-54). On magnetic resonance imaging (MRI), oligodendrogliomas were associated with smooth margins and T1-weighted hypointensity compared to astrocytomas (odds ratio [OR], 42.5; 95% CI, 2.42-744.97; P = .04; OR, 45.5; 95% CI, 5.78-333.33; P < .001, respectively) and undefined gliomas (OR, 84; 95% CI, 3.43-999.99; P = .02; OR, 32.3; 95% CI, 2.51-500.00; P = .008, respectively) and were more commonly in contact with the ventricles than astrocytomas (OR, 7.47; 95% CI, 1.03-53.95; P = .049). Tumor spread to neighboring brain structures was associated with high-grade glioma (OR, 6.02; 95% CI, 1.06-34.48; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with gliomas have poor outcomes, but risk factors identified in survival analysis inform prognosis and the newly identified MRI characteristics could refine diagnosis of tumor type and grade.

Antigens under cover-The preservation and demasking of selected antigens for successful poststaining immunocytochemistry of effusion, brain smears, and lymph node aspirates.

BACKGROUND: In clinical cytology, the applicability of an ancillary test such as immunocytochemistry is too often limited by low sample volume, poor cell representation, and sample preservation. Diagnosticians often read Romanowsky-stained cytology, although specific techniques such as immunocytochemistry are often essential for a definitive diagnosis. OBJECTIVES: The goal of the present study aimed to investigate if immunocytochemistry on previously-stained cytologic specimens was possible. Different pretreatments were examined to determine which treatment preserved antigenicity best. METHODS: One hundred and twenty-two impression smears and 64 fine-needle aspirate preparations of brain and lymph nodes were processed and evaluated microscopically. The impact of staining cytologic preparations with a modified Wright's stain, using a destaining method, performing a coverslipping and decoverslipping process, and subjecting smears to a microwave treatment (MWT) were examined for the immunolabeling of selected nuclear, cytoplasmic, and plasmalemmal antigens, as well as intracellular feline coronavirus (FCoV). Biotinylated secondary antibodies were used, and the bound primary antibody was visualized using an ABC amplification kit. RESULTS: Cellular antigens were reliably detected with immunocytochemistry after smears were stained with a Romansky stain and were coverslipped early after staining and stayed coverslipped until immediately before immunolabeling. The staining intensity reached the same levels as that of the controls if the films underwent MWT in citrate buffer. In contrast, FCoV antigen detection was abolished after any physicochemical interference. CONCLUSIONS: Poststaining immunocytochemistry represents a practical tool for additional investigations on prestained cytologic specimens when searching for cellular antigens. Paired untreated samples should be kept in case the workup requires testing for more vulnerable viral antigens.

Detection of feline coronavirus in cerebrospinal fluid for diagnosis of feline infectious peritonitis in cats with and without neurological signs.

OBJECTIVES: The objective of this study was to evaluate the sensitivity and specificity of a real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) detecting feline coronavirus (FCoV) RNA in cerebrospinal fluid (CSF) of cats with and without neurological and/or ocular signs for the diagnosis of feline infectious peritonitis (FIP). METHODS: This prospective case-control study included 34 cats. Nineteen cats had a definitive histopathological diagnosis of FIP (seven of these with neurological and/or ocular signs), and 15 cats had other diseases but similar clinical signs (three of these with neurological and/or ocular signs). Real-time RT-PCR was performed on the CSF of all cats, and sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were calculated. RESULTS: Real-time RT-PCR of CSF showed a specificity of 100% in diagnosing FIP, a sensitivity of 42.1%, a PPV of 100% and an NPV of 57.7%. The sensitivity of the real-time RT-PCR of CSF in cats with neurological and/or ocular signs was 85.7%. CONCLUSIONS AND RELEVANCE: Although it is known that RT-PCR can give false positive results, especially if performed using serum or plasma, this real-time RT-PCR detecting FCoV RNA in CSF can be considered a reliable specific tool for the diagnosis of FIP. If only cats with neurological involvement are evaluated, the sensitivity of this real-time RT-PCR in CSF is also high.

Inferior cerebellar hypoplasia resembling a Dandy-Walker-like malformation in purebred Eurasier dogs with familial non-progressive ataxia: a retrospective and prospective clinical cohort study.

Cerebellar malformations can be inherited or caused by insults during cerebellar development. To date, only sporadic cases of cerebellar malformations have been reported in dogs, and the genetic background has remained obscure. Therefore, this study`s objective was to describe the clinical characteristics, imaging features and pedigree data of a familial cerebellar hypoplasia in purebred Eurasier dogs. A uniform cerebellar malformation characterized by consistent absence of the caudal portions of the cerebellar vermis and, to a lesser degree, the caudal portions of the cerebellar hemispheres in association with large retrocerebellar fluid accumulations was recognized in 14 closely related Eurasier dogs. Hydrocephalus was an additional feature in some dogs. All dogs displayed non-progressive ataxia, which had already been noted when the dogs were 5-6 weeks old. The severity of the ataxia varied between dogs, from mild truncal sway, subtle dysmetric gait, dysequilibrium and pelvic limb ataxia to severe cerebellar ataxia in puppies and episodic falling or rolling. Follow-up examinations in adult dogs showed improvement of the cerebellar ataxia and a still absent menace response. Epileptic seizures occurred in some dogs. The association of partial vermis agenesis with an enlarged fourth ventricle and an enlarged caudal (posterior) fossa resembled a Dandy-Walker-like malformation in some dogs. Pedigree analyses were consistent with autosomal recessive inheritance.

Hippocampal sclerosis in feline epilepsy.

Hippocampal sclerosis (HS) refers to loss of hippocampal neurons and astrogliosis. In temporal lobe epilepsy (TLE), HS is a key factor for pharmacoresistance, even though the mechanisms are not quite understood. While experimental TLE models are available, there is lack of models reflecting the natural HS development. Among domestic animals, cats may present with TLE-like seizures in natural and experimental settings. With this study on the prevalence, segmental pattern and clinicopathological correlates of feline HS, we evaluated the translational value for human research. Evaluation schemes for human brains were applied to epileptic cats. The loss of neurons was morphometrically assessed and the degree of gliosis was recorded. Hippocampal changes resembling human HS were seen in about one third of epileptic cats. Most of these were associated with infiltrative diseases such as limbic encephalitis. Irrespective of the etiology and semiology of seizures, total hippocampal sclerosis was the most prevalent form seen in epileptic animals. Other HS types also occur at varying frequencies. Segmental differences to human HS can be explained by species-specific synaptic connectivities and a different spectrum of etiologies. All these variables require consideration when translating results from feline studies regarding seizure-associated changes of the temporal lobe and especially HS.

Clinical course of acute canine polyradiculoneuritis following treatment with human IV immunoglobulin.

Treatment of dogs with acute canine polyradiculoneuritis (ACP) is restricted to physical rehabilitation and supportive care. In humans with Guillain-Barré syndrome, the counterpart of ACP, randomized trials show that IV immunoglobulin (IVIg) speeds recovery. The authors of the current study hypothesized that dogs with ACP would tolerate IVIg well and recover faster than dogs managed with supportive treatment only. Sixteen client-owned dogs with ACP were treated with IVIg, and 14 client-owned dogs served as a retrospective control group. Diagnosis was confirmed using clinical features, electrodiagnostics, cerebrospinal fluid analysis, and muscle/nerve biopsies. The duration of the initial progressive phase, the time from IVIg administration until the dogs were ambulating without assistance, and the duration of the complete episode were evaluated. Adverse reactions (anaphylaxis, mild hematuria) were observed in two dogs. Dogs treated with IVIg were ambulating without assistance after a median of 27.5 days (range, 15-127 days) from onset of clinical signs. The control group was ambulatory without assistance at a median of 75.5 days (range, 5-220 days). Even though this result is not statistically significant, there is a clear trend toward faster recovery in dogs treated with IVIg.

Axonal neuropathy with unusual clinical course in young Snowshoe cats.

Neuropathies in cats are mostly acquired. In comparison to the dog, only very few inherited forms have been described. This case report describes the clinical and diagnostic findings of a suspected inherited feline axonal neuropathy with a very unique clinical course. Two young related male Snowshoe cats were presented with an initially progressive history of recurrent pelvic limb weakness. Electrodiagnostic investigations suggested an axonopathy and muscle-nerve biopsies confirmed axonal degeneration. Over the following 2 years both cats stabilised without any specific treatment, and repeat electrodiagnostic investigations and muscle biopsy in one cat confirmed the tendency for remission.

Clinical and magnetic resonance imaging findings in 92 cats with clinical signs of spinal cord disease.

Medical records of 92 cats presented with clinical signs of spinal cord disease, which had undergone magnetic resonance imaging (MRI), were reviewed. The cats were grouped into seven categories based upon the diagnosis suggested by results of MRI, cerebrospinal fluid analysis and other diagnostic procedures: neoplastic (n=25), inflammatory or infectious (n=13), traumatic (n=8), vascular (n=6), degenerative (n=5), anomalous (n=3) and those with an unremarkable MRI (n=32). There were two independent predictors of abnormal MRI findings: severity of clinical signs and presence of spinal pain. Abnormal MRI findings and speed of onset of disease were significantly associated with survival. For the 32 cats with unremarkable MRI findings, only nine died due to spinal disease and, therefore, the median survival time (MST) was not reached (lower 95% confidence interval (CI)=970 days). For the 60 cats with abnormal MRI findings, 37 died due to their disease and the MST was 138 days (95% CI: 7-807).

The efficacy and tolerability of levetiracetam in pharmacoresistant epileptic dogs.

Twenty-two dogs with idiopathic epilepsy which were pharmacoresistant to phenobarbitone and bromide were treated with levetiracetam as an add-on medication. Records of eight dogs were used retrospectively to determine a safe, efficient levetiracetam dosage. Fourteen dogs were entered into a prospective, open label, non-comparative study. After 2 months of levetiracetam oral treatment (10 mg/kg TID), 8/14 dogs responded significantly to the treatment and seizure frequency was reduced by 50%. In dogs that remained refractory, the dosage was increased to 20 mg/kg TID for 2 months. One further dog responded to levetiracetam treatment. Levetiracetam responders had a significant decrease in seizure frequency of 77% (7.9+/-5.2 to 1.8+/-1.7 seizures/month) and a decrease in seizure days per month of 68% (3.8+/-1.7 to 1.2+/-1.1 seizure days/month). However, 6/9 responders experienced an increase in seizure frequency and seizure days after 4-8 months continuing with the levetiracetam treatment at the last effective dosage. Levetiracetam was well tolerated by all dogs and sedation was the only side-effect reported in just one of the 14 dogs.

Clinical and magnetic resonance imaging characteristics of quadrigeminal cysts in dogs.

BACKGROUND: Quadrigeminal cysts (QC) are the most common intracranial intra-arachnoid cysts in dogs, primarily affecting small breeds. Clinical significance is controversial. HYPOTHESIS: Male, brachycephalic, small breed dogs are predisposed to QC, and objective measurement of parenchymal compression can distinguish clinically relevant QC from incidental findings. ANIMALS: A total of 4,100 client-owned dogs. METHODS: A retrospective study that recorded signalment, history, clinical signs, and magnetic resonance imaging features. The degree of brain compression was evaluated in the presence of relevant clinical signs. The percentage compression of cerebellum and forebrain was calculated by comparing the expected to the actual diameter and longitudinal dimension, respectively. RESULTS: QC were diagnosed in 28 dogs, of which 21 (75%) were small breed dogs. Fifteen dogs (54%) were brachycephalic. Eighteen dogs were male, and 10 were female. Cerebellar, occipital lobe, or compression in both areas occurred in 86% (24/28 dogs). Clinical signs included focal and generalized seizures in 5 dogs and cerebellar signs in 6 dogs. Mean occipital lobe compression was 17% (SD = 4) in clinically affected and 10% (SD = 3) in normal dogs (P = .006). Occipital lobe compression >14% was always associated with clinical signs. The mean cerebellar compression was 18%, but there was no association between compression and clinical signs. The animals were more likely to develop clinical signs if both areas were compressed (P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Parenchymal compression by QC can be incidental, and other central nervous system diseases must be excluded when assessing the clinical significance of QC. However, occipital lobe compression over 14% is likely to cause clinical signs.

Subfascial seroma causing compressive myelopathy after cervical dorsal laminectomy.

Dorsal surgical approach to the cervical vertebral canal is indicated for a variety of spinal cord diseases. Compressive myelopathy due to subfascial seroma following dorsal laminectomy has not previously been documented in dogs. We describe neurologic findings, magnetic resonance (MR) imaging characteristics and clinical outcome in a young Rottweiler experiencing this complication after a successful dorsal decompression for treatment of cervical stenotic myelopathy. MR imaging allowed detection of pockets of high signal intensity material on T2-weighted images and low signal intensity in T1-weighted images. Prompt surgical revision and drainage allowed complete recovery.