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PurposeSpontaneously occurring glioma in pet dogs is increasingly recognized as a valuable translational model for human glioblastoma. Canine high-grade glioma and human glioblastomas share many molecular similarities, including the accumulation of immunosuppressive regulatory T cells (Tregs) that inhibit anti-tumor immune responses. Identifying in dog mechanisms responsible for Treg recruitment may afford to target the cellular population driving immunosuppression, the results providing a rationale for translational clinical studies in human patients. Our group has previously identified C-C motif chemokine 2 (CCL2) as a glioma-derived T-reg chemoattractant acting on chemokine receptor 4 (CCR4) in a murine orthotopic glioma model. Recently, we demonstrated a robust increase of CCL2 in the brain tissue of canine patients bearing high-grade glioma.MethodsWe performed a series of in vitro experiments using canine Tregs and patient-derived canine glioma cell lines (GSC 1110, GSC 0514, J3T-Bg, G06A) to interrogate the CCL2-CCR4 signaling axis in the canine.ResultsWe established a flow cytometry gating strategy for identifying and isolating FOXP3+ Tregs in dogs. The canine CD4 + CD25high T-cell population was highly enriched in FOXP3 and CCR4 expression, indicating they are bona fide Tregs. Canine Treg migration was enhanced by CCL2 or by glioma cell line-derived supernatant. Blockade of the CCL2-CCR4 axis significantly reduced migration of canine Tregs. CCL2 mRNA was expressed in all glioma cell lines, and expression increased when exposed to Tregs but not CD4 + helper T-cells.ConclusionOur study validates CCL2-CCR4 as a bi-directional Treg-glioma immunosuppressive and tumor-promoting axis in canine high-grade glioma.

BackgroundReports of motor polyneuropathies in young cats are scarce. Further, in-depth electrophysiologic evaluation to confirm a motor polyneuropathy in young cats of various breeds other than 2 Bengal cats is lacking.Hypothesis/objectivesTo confirm a motor polyneuropathy in young cats of various breeds.AnimalsFive young cats with heterogenous chronic or relapsing episodes of weakness.MethodsRetrospective case series. Cats were presented for evaluation of generalized neuromuscular disease and underwent electrophysiologic examination including electromyography, nerve conduction, and repetitive nerve stimulation. Minimum database and muscle and nerve biopsy analyses were carried out. Descriptive statistics were performed.ResultsDisease onset was at 3 months to 1 year of age and in 5 breeds. The most common clinical sign (5 of 5 cats) was weakness. Additional neurologic deficits consisted of palmigrade and plantigrade posture (4/4), low carriage of the head and tail (4/4), and variable segmental reflex deficits (5/5). Motor nerve conduction studies were abnormal for the ulnar (4/4), peroneal (5/5), and tibial (2/2) nerves (increased latencies, reduced amplitudes, slow velocities). A marked decrement was observed on repetitive nerve stimulation of the peroneal nerve in 3 cats for which autoimmune myasthenia gravis was ruled out. All sensory nerve conduction studies were normal. Histologic evaluation of muscle and nerve biopsies supported heterogenous alterations consistent with motor polyneuropathy with distal nerve fiber loss.Conclusions and clinical importanceHeterogenous motor polyneuropathies should be considered in young cats of any breed and sex that are presented with relapsing or progressive generalized neuromuscular disease.

BackgroundCanine necrotizing meningoencephalitis (NME) is a fatal, noninfectious inflammatory disease of unknown etiology. NME has been reported only in a small number of dog breeds, which has led to the presumption that it is a breed-restricted disorder.Hypothesis/objectivesOur objective was to describe histopathologically confirmed NME in dog breeds in which the condition has not been reported previously and to provide preliminary evidence that NME affects a wider spectrum of dog breeds than previously reported.AnimalsFour dogs with NME.MethodsArchives from 3 institutions and from 1 author's (BS) collection were reviewed to identify histopathologically confirmed cases of NME in breeds in which the disease has not been reported previously. Age, sex, breed, survival from onset of clinical signs, and histopathologic findings were evaluated.ResultsNecrotizing meningoencephalitis was identified in 4 small dog breeds (Papillon, Shih Tzu, Coton de Tulear, and Brussels Griffon). Median age at clinical evaluation was 2.5 years. Histopathologic abnormalities included 2 or more of the following: lymphoplasmacytic or histiocytic meningoencephalitis or encephalitis, moderate-to-severe cerebrocortical necrosis, variable involvement of other anatomic locations within the brain (cerebellum, brainstem), and absence of detectable infectious agents.Conclusions and clinical importanceUntil now, NME has only been described in 5 small dog breeds. We document an additional 4 small breeds previously not shown to develop NME. Our cases further illustrate that NME is not a breed-restricted disorder and should be considered in the differential diagnosis for dogs with signalment and clinical signs consistent with inflammatory brain disease.

Results of a neurological examination usually permit localisation of a vestibular disorder to either the central or peripheral parts of the vestibular system. Many different disorders located in the same part of the vestibular system will produce similar clinical signs. Therefore, additional diagnostic tests beyond a neurological examination are required in order to make an accurate diagnosis. The objectives of this review are to outline a diagnostic approach for disorders affecting the feline vestibular system, and to summarise the clinically important features of frequently diagnosed diseases affecting the vestibular system of cats.

Objectives: The aim of this study was to prospectively evaluate in a randomized, triple-masked, placebo-controlled trial, outcomes for kittens with ocular manifestations of infectious upper respiratory disease (IURD) treated with an ophthalmic and oral antibiotic only vs those also treated with famciclovir., Methods: Kittens were stratified into three age (1 to <4, 4 to <8 or 8-12 weeks) and two disease severity ('mild' [total disease score 1-11] or 'severe' [total disease score 12-23]) groups and randomized to receive approximately 5 mg/kg doxycycline either with placebo (group D) or with approximately 90 mg/kg famciclovir (group DF) PO q12h. Caregivers scored clinical signs once daily for 21 days. Ophthalmic examinations and scoring by veterinarians were completed on days 1 and 21. Ophthalmic and clinical resolution were defined as scores of zero for all ocular signs and all ocular and respiratory signs, respectively. Ophthalmic and clinical recovery were defined by absence of active inflammation., Results: For kittens with mild disease, those in group D were slower than those in group DF to achieve clinical recovery ( P  = 0.049) and clinical resolution ( P  = 0.030), but not ophthalmic recovery ( P  = 0.064) or ophthalmic resolution ( P  = 0.089). Kittens with mild disease and receiving famciclovir achieved predicted 75% clinical resolution 4-5 days earlier than kittens with mild disease and receiving doxycycline alone, and kittens with severe disease (regardless of treatment group). Significantly fewer kittens in group DF developed corneal disease than in group D ( P  = 0.016). All five kittens whose clinical signs worsened sufficiently to be removed from the study were in group D., Conclusions and Relevance: The addition of famciclovir to standard antibiotic treatment may reduce corneal disease, length of stay and time to adoption for shelters and rescue groups, thereby increasing capacity for care. Early administration of famciclovir in kittens exhibiting mild ocular manifestations of IURD may be preferable to delaying this treatment until the disease progresses to a severe stage., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To compare the effects of oral pregabalin versus gabapentin on sedation quality and anesthesia recovery times in cats in a typical perioperative setting., Animals: 50 healthy cats with > 1 kg body weight presenting for elective surgery., Methods: In this randomized, prospective clinical trial, cats presenting to the University of California-Davis Veterinary Medical Teaching Hospital were assigned to receive buprenorphine 0.02 mg/kg IM followed by 1 of 2 oral sedation treatments: pregabalin 4 mg/kg or gabapentin 10 mg/kg. Cats were then anesthetized using a standardized protocol. Physical examination parameters and behavioral scores were measured by 2 treatment-blinded veterinarians to compare sedation levels before and after drug administration. Inadequate sedation for handling or IV catheter placement was addressed by dexmedetomidine administration. After surgery was completed, anesthesia recovery times and quality were assessed by the same veterinarians. The effects of pregabalin versus gabapentin on body temperature, respiratory rate, and heart rate were analyzed using Student t tests; behavioral assessments were analyzed using Wilcoxon signed-rank tests; and drug treatment effects on dexmedetomidine sedation rescue and frequency of delirium during anesthetic recovery were analyzed using Fisher exact tests. A P < .05 indicated statistical significance., Results: There was no significant difference in change of physiologic parameters or sedation scores before and after sedation between groups. The need for rescue sedation for IV catheter placement and the incidence of emergence delirium were infrequent and similar for both treatments., Clinical Relevance: At the doses studied, oral pregabalin and gabapentin produced indistinguishable effects as adjunctive perioperative sedation agents in cats.

Background: Cytosine arabinoside (Ara-C) is a nucleoside analog prodrug utilized for immunomodulatory effects mediated by its active metabolite Ara-CTP. Optimal dosing protocols for immunomodulation in dogs have not been defined. Cytarabine ocfosfate (CO) is a lipophilic prodrug of Ara-C that can be administered PO and provides prolonged serum concentrations of Ara-C., Objectives: Provide pharmacokinetic data for orally administered CO and determine accumulation and functional consequences of Ara-CTP within peripheral blood leukocytes., Animals: Three healthy female hound dogs and 1 healthy male Beagle., Methods: Prospective study. Dogs received 200 mg/m 2 of CO PO q24h for 7 doses. Serum and cerebrospinal fluid (CSF) CO and Ara-C concentrations were measured by liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Complete blood counts, flow cytometry, and leukocyte activation assays were done up to 21 days. Incorporation of Ara-CTP within leukocyte DNA was determined by LC-MS/MS., Results: Maximum serum concentration (C max ) for Ara-C was 456.1-724.0 ng/mL (1.88-2.98 μM) and terminal half-life was 23.3 to 29.4 hours. Cerebrospinal fluid: serum Ara-C ratios ranged from 0.54 to 1.2. Peripheral blood lymphocyte concentrations remained within the reference range, but proliferation rates poststimulation were decreased at 6 days. Incorporation of Ara-CTP was not saturated and remained >25% of peak concentration at 13 days., Conclusions and Clinical Importance: Oral CO may produce prolonged serum Ara-C half-lives at concentrations sufficient to induce functional changes in peripheral leukocytes and is associated with prolonged retention of DNA-incorporated Ara-CTP. Application of functional and active metabolite assessment is feasible and may provide more relevant data to determine optimal dosing regimens for Ara-C-based treatments., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Non-human animals are natural hosts for the virus causing COVID-19 (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) and a diversity of species appear susceptible to infection. Cats are of particular concern because of their close affiliation with humans and susceptibility to infection. Cats also harbour feline enteric coronavirus (FECV). Our objectives were to document the prevalence of SARS-CoV-2 and FECV in feline populations with high turnover and movement among households in the Central Valley of California, USA., Methods: A cross-sectional study of 128 shelter and foster cats and kittens in the Central Valley of California was performed from July to December 2020. PCR was performed on rectal and oropharyngeal samples to detect SARS-CoV-2 RNA and on rectal samples to detect FECV RNA., Results: Among 163 rectal and oropharyngeal fluid samples gathered from sheltered and fostered cats and kittens in central California, SARS-CoV-2 nucleic acids were not detected from any cat or kitten. In contrast, FECV nucleic acids were detected in 18% of shelter-housed cats; 83% of these positive samples were collected from cats housed in adjacent cages., Conclusions: These data may be helpful when considering the allocation of resources to minimise the harm of FECV and SARS-CoV-2 in household pets and shelter environments., Competing Interests: The authors declare they have no conflicts of interest., (© 2023 The Authors. Veterinary Record Open published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the intratumoral concentration of several known GAM-derived pro-tumorigenic molecules in high-grade oligodendrogliomas compared to that in a normal brain. Our analysis demonstrated marked intra- and intertumoral heterogeneity of GAM infiltration. Correspondingly, we observed significant variability in the intratumoral concentrations of several GAM-associated molecules, unlike what we previously observed in high-grade astrocytomas. However, high-grade oligodendroglioma tumor homogenates (n = 6) exhibited an increase in the pro-tumorigenic molecules hepatocyte growth factor receptor (HGFR) and vascular endothelial growth factor (VEGF), as we observed in high-grade astrocytomas. Moreover, neoplastic oligodendrocytes displayed robust expression of GAL-3, a chimeric galectin implicated in driving immunosuppression in human glioblastoma. While this work identifies shared putative therapeutic targets across canine glioma subtypes (HGFR, GAL-3), it highlights several key differences in the immune landscape. Therefore, a continued effort to develop a comprehensive understanding of the immune microenvironment within each subtype is necessary to inform therapeutic strategies going forward.

Clostridium piliforme , the agent of Tyzzer disease, has traditionally not been considered a major pathogen of cats. We queried the database of the Pathology Service of the Veterinary Medical Teaching Hospital, University of California-Davis, for kittens <6-mo-old autopsied between 2000-2021 that had colitis, hepatitis, and/or myocarditis; 37 cases met the search criteria. Sections of colon, liver, and heart from these 37 cats were stained with modified Steiner; 19 of 37 (51%) cases had intraepithelial, Steiner-positive rods compatible with C. piliforme in at least one organ, confirming Tyzzer disease. The affected age range was 7-42 d (median: 17.5 d). Eighteen were orphaned kittens. Colitis was the major lesion (18 of 19) followed by random hepatitis (11 of 19). Perianal dermatitis with intraepithelial stacked rods was seen in 2 of 19. Myocarditis was not evident in any of the cases. A PCR assay for C. piliforme on 10 selected cases using formalin-fixed, paraffin-embedded (FFPE) blocks was positive or suspected in colon (5 of 10), liver (5 of 10), and heart (1 of 10). The modified Steiner stain was more sensitive in the detection of bacteria than PCR on FFPE samples. Fifteen kittens had comorbidities. A weakened immune state caused by maternal, environmental, infectious, and/or nutritional causes is speculated to have contributed to disease onset. We found that Tyzzer disease is more common than previously believed in orphaned kittens and should be considered in kittens with colitis and/or hepatitis.

Objectives: The aim of this study was to retrospectively evaluate the signalment, treatment, surgical technique and outcomes for feline symblepharon., Methods: A retrospective medical record review and standardized grading of clinical descriptions and photographs was undertaken., Results: Forty kittens (54 eyes) aged 3-46 weeks had symblepharon of five types in various combinations: eyelid deformation (24 kittens; 32 eyes); ankyloblepharon (four kittens; four eyes); conjunctiva-to-conjunctiva (11 kittens; 12 eyes); third eyelid-to-conjunctiva (24 kittens; 29 eyes); and corneoconjunctival adhesions (14 kittens; 16 eyes). At initial presentation, 23 (43%) eyes were affected by one type of symblepharon, 25 (46%) eyes by two types and six (11%) eyes by three types; 11 (20%) corneas were ulcerated. Twenty-four (44%) eyes of 18 (45%) kittens were managed medically. Surgery was performed under general anesthesia/sedation (30 occasions) or topical anesthesia (21 occasions) on 30 (56%) eyes of 22 kittens; 12 eyes (40%) underwent multiple surgeries. Four techniques were commonly employed: separation of conjunctival-to-conjunctival adhesions ± eyelid margins (14 eyes); resection of third eyelid adhesions ± temporary tacking of the third eyelid (modified Arlt's pterygium technique; 18 eyes); en bloc resection of the third eyelid (two eyes); and separation of corneoconjunctival adhesions (14 eyes). Median duration of follow-up was 55 days (range 1-1051). Median symblepharon grade in kittens treated surgically improved for all types except corneoconjunctival symblepharon. Median symblepharon grade in kittens receiving medical management remained the same or improved. Corneoconjunctival symblepharon opacity decreased for eyes treated surgically but increased for eyes treated medically. Three eyes were enucleated due to complications of corneoconjunctival symblepharon. At final presentation, symblepharon persisted in 46 (85%) eyes; however, menace response was evident in 13/16 eyes and dazzle reflex in 23/23 eyes., Conclusions and Relevance: Symblepharon is a heterogeneous group of conditions with diverse anatomic involvement, clinical appearance and impact, optimal treatment and prognosis for vision.

Clopidogrel is converted to its active metabolite by cytochrome P450 isoenzymes and irreversibly inhibits platelet activation by antagonizing the adenosine-diphosphate (ADP) receptor. It is frequently used in cats with hypertrophic cardiomyopathy (HCM) to prevent thromboembolic complications. However, significant interpatient variability of the response to clopidogrel therapy has been suspected. In this study, we assessed the impact of single nucleotide polymorphisms (SNPs) within ADP receptor (P2RY1, P2RY12) and cytochrome P450 isoenzyme (CYP2C41) genes on platelet inhibition by clopidogrel administration in cats with HCM. Forty-nine cats completed the study, and blood samples were obtained before and after clopidogrel therapy to assess the degree of platelet inhibition based on flow cytometry and whole blood platelet aggregometry. Plasma concentrations of clopidogrel metabolites were measured after the last dose of clopidogrel. Whole blood platelet aggregometry revealed a significant reduction of platelet inhibition by clopidogrel in cats with the P2RY1:A236G and the P2RY12:V34I variants. The association with the P2RY1:A236G variant and clopidogrel resistance remained significant after adjustment for multiple comparisons. This study demonstrated that a genetic polymorphism in the P2RY1 gene altered response to clopidogrel therapy and suggests that clinicians may consider alternative or additional thromboprophylactic therapy in cats with the P2RY1:A236G variant.

Objectives: Assessment of heart size in kittens is important, and there is a need for reference intervals (RIs) to prevent misinterpretation of cardiomegaly in this patient population. The purpose of this study was to generate RIs for echocardiographic and radiographic quantification of cardiac size in healthy kittens., Methods: In total, 88 kittens aged 6-16 weeks were enrolled in this study. Physical examination, and radiographic and echocardiographic evaluations were performed without sedation. Thoracic radiographs and echocardiographic images were measured to establish RIs for vertebral heart score (VHS), cardiac thoracic ratio (CTR) and multiple echocardiographic variables. N-terminal pro B-type natriuretic peptide (NT-proBNP) was measured. Statistical correlations between echocardiographic parameters and age, body weight and sex were all evaluated and RIs were generated., Results: Low-grade heart murmurs were appreciated in 26/88 kittens (29.5%). Kittens had a median VHS of 9.5 vertebrae (95% RI 8.0-10.9) and a median CTR of 67.2% (95% RI 54.4-79.8%). Measured NT-proBNP levels were comparable to healthy adult cats with a median of 31 pmol/l (upper reference limit 75 pmol/l). Multiple moderate-to-strong correlations between body weight and age with various echocardiographic parameters were observed and allometric scaling was performed for body weight. RIs for echocardiographic parameters were generated based on patient weight using allometric scaling formulas. Tricuspid valve regurgitation was a common finding and was present in 37.5% (n = 33) of the kittens., Conclusions and Relevance: This study establishes RIs for thoracic radiograph assessment, echocardiography and cardiac biomarkers in kittens, which fills a critical gap in the veterinary literature. The VHS reported in this study is higher than previously reported for adult cats.

Over 94 million domestic cats are susceptible to cancers and other common and rare diseases. Whole exome sequencing (WES) is a proven strategy to study these disease-causing variants. Presented is a 35.7 Mb exome capture design based on the annotated Felis&#95;catus&#95;9.0 genome assembly, covering 201,683 regions of the cat genome. Whole exome sequencing was conducted on 41 cats with known and unknown genetic diseases and traits, of which ten cats had matching whole genome sequence (WGS) data available, used to validate WES performance. At 80 × mean exome depth of coverage, 96.4% of on-target base coverage had a sequencing depth > 20-fold, while over 98% of single nucleotide variants (SNVs) identified by WGS were also identified by WES. Platform-specific SNVs were restricted to sex chromosomes and a small number of olfactory receptor genes. Within the 41 cats, we identified 31 previously known causal variants and discovered new gene candidate variants, including novel missense variance for polycystic kidney disease and atrichia in the Peterbald cat. These results show the utility of WES to identify novel gene candidate alleles for diseases and traits for the first time in a feline model.

Dogs provide highly valuable models of human disease due to the similarity in phenotype presentation and the ease of genetic analysis. Seven Saluki puppies were investigated for neurological abnormalities including seizures and altered behavior. Magnetic resonance imaging showed a diffuse, marked reduction in cerebral cortical thickness, and symmetrical T2 hyperintensity in specific brain regions. Cerebral cortical atrophy with vacuolation (status spongiosus) was noted on necropsy. Genome-wide association study of 7 affected and 28 normal Salukis revealed a genome-wide significantly associated region on CFA 35. Whole-genome sequencing of three confirmed cases from three different litters revealed a homozygous missense variant within the aldehyde dehydrogenase 5 family member A1 ( ALDH5A1 ) gene (XM&#95;014110599.2: c.866G>A; XP&#95;013966074.2: p.(Gly288Asp). ALDH5A1 encodes a succinic semialdehyde dehydrogenase (SSADH) enzyme critical in the gamma-aminobutyric acid neurotransmitter (GABA) metabolic pathway. Metabolic screening of affected dogs showed markedly elevated gamma-hydroxybutyric acid in serum, cerebrospinal fluid (CSF) and brain, and elevated succinate semialdehyde in urine, CSF and brain. SSADH activity in the brain of affected dogs was low. Affected Saluki dogs had striking similarities to SSADH deficiency in humans although hydroxybutyric aciduria was absent in affected dogs. ALDH5A1 -related SSADH deficiency in Salukis provides a unique translational large animal model for the development of novel therapeutic strategies.

Polyneuropathy is defined as the simultaneous dysfunction of several peripheral nerves. In dogs, a number of breeds are predisposed to a variety of immune-mediated and/or degenerative inherited forms of polyneuropathy, with laryngeal paralysis and/or megaesophagus as important clinical features of many of these conditions. This case series describes degenerative and inflammatory polyneuropathies in 7 young Siberian huskies that were categorized based on clinicopathological characteristics as follows: (1) slowly progressive laryngeal paralysis and megaesophagus caused by primary axonal degeneration with large fiber loss (n = 2); (2) slowly progressive polyneuropathy without megaesophagus or laryngeal paralysis caused by primary axonal degeneration with large fiber loss (n = 2); (3) acute inflammatory demyelinating neuropathy causing sensory, motor and autonomic nerve deficits (n = 2); and (4) ganglioradiculitis (sensory neuronopathy; n = 1). Based on the predominantly young age at onset, slow progression, relatedness of affected dogs, and clinical and pathological similarities with inherited neuropathies reported in other dog breeds, a hereditary basis for the degenerative polyneuropathies in Siberian huskies is suspected. However, 5 different mutations in 3 genes known to cause polyneuropathy in other dog breeds ( NDRG1 , ARHGEF10 , or RAB3GAP1 ) were not detected in the affected Siberian huskies suggesting that more genetic variants remain to be identified. This study highlights the varied underlying lesions of polyneuropathies in young Siberian huskies.

Background: Histiocytic sarcoma affecting the central nervous system (CNS HS) in dogs may present as primary or disseminated disease, often characterized by inflammation. Prognosis is poor, and imaging differentiation from other CNS tumors can be problematic., Objective: To characterize the clinicopathological inflammatory features, breed predisposition, and survival in dogs with CNS HS., Animals: One hundred two dogs with HS, 62 dogs with meningioma., Methods: Retrospective case series. Records were reviewed for results of cerebrospinal fluid (CSF) analysis, CBC, treatment, and outcome data., Results: Predisposition for CNS HS was seen in Bernese Mountain Dogs, Golden Retrievers, Rottweilers, Corgis, and Shetland Sheepdogs (P ≤ .001). Corgis and Shetland Sheepdogs had predominantly primary tumors; Rottweilers had exclusively disseminated tumors. Marked CSF inflammation was characteristic of primary rather than disseminated HS, and neoplastic cells were detected in CSF of 52% of affected dogs. Increased neutrophil to lymphocyte ratios were seen in all groups relative to controls (P <.008) but not among tumor subtypes. Definitive versus palliative treatment resulted in improved survival times (P < .001), but overall prognosis was poor., Conclusions and Clinical Importance: Clinicopathological differences between primary and disseminated HS suggest that tumor biological behavior and origin may be different. Corgis and Shetland Sheepdogs are predisposed to primary CNS HS, characterized by inflammatory CSF. High total nucleated cell count and the presence of neoplastic cells support the use of CSF analysis as a valuable diagnostic test. Prognosis for CNS HS is poor, but further evaluation of inflammatory mechanisms may provide novel therapeutic opportunities., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission that may be presynaptic, synaptic, or postsynaptic. Causative mutations have been identified in 4 breeds including the Labrador Retriever, Jack Russell Terrier, Heideterrier, and Danish Pointing Dog., Hypothesis/objective: Clinical and genetic characterization of a neuromuscular disorder in Golden Retriever (GR) puppies., Animals: Four GR puppies from California were evaluated for generalized muscle weakness beginning at weaning. Biological specimens were collected from the affected puppies, and familial information was obtained. Blood or buccal swabs were obtained from 63 unaffected GRs., Methods: Complete physical, neurological, electrodiagnostic, and histological evaluations and biochemical quantification of muscle acetylcholine receptors were performed. Polymerase chain reaction was used to amplify the 17 exons of COLQ, and sequences were obtained by Sanger sequencing. Variant frequency was assessed in unrelated GRs and a public database., Results: Clinical, neurological, and electrodiagnostic evaluations confirmed a disorder of neuromuscular transmission in a GR family. Sequencing of all exons and splice sites of a primary candidate gene, COLQ, identified a point mutation that predicts an amino acid substitution (G294R). The primary COLQ transcript was absent from affected muscle samples. All affected puppies were homozygous for the mutation, which was not detected outside this GR family or in other breeds., Conclusions and Clinical Importance: We confirmed the diagnosis of a CMS in GR puppies and identified a novel COLQ mutation. The COLQ gene encodes the collagenous tail of acetylcholinesterase, the enzyme responsible for termination of skeletal muscle contraction by clearing acetylcholine at the neuromuscular junction. Clinicians and breeders should be aware of this CMS in GR puppies with an early onset of weakness., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

A 5-month-old female pit bull terrier dog evaluated for ataxia, progressive regurgitation, and recurrent aspiration pneumonia had markedly elevated creatine kinase activity, non-inflammatory generalized myopathy, and severe esophageal dysmotility. A narrow-field total laryngectomy was performed. The dog is doing well 30 months after surgery, and no longer has episodes of aspiration pneumonia, despite intermittent regurgitation. This case represents the first application of total laryngectomy for the prevention of chronic recurrent aspiration pneumonia in the dog.

Necrotizing meningoencephalitis (NME) affects toy and small breed dogs causing progressive, often fatal, inflammation and necrosis in the brain. Genetic risk loci for NME previously were identified in pug dogs, particularly associated with the dog leukocyte antigen (DLA) class II complex on chromosome 12, but have not been investigated in other susceptible breeds. We sought to evaluate Maltese and Chihuahua dogs, in addition to pug dogs, to identify novel or shared genetic risk factors for NME development. Genome-wide association testing of single nucleotide polymorphisms (SNPs) in Maltese dogs with NME identified 2 regions of genome-wide significance on chromosomes 4 (chr4:74522353T>A, p = 8.1×10-7) and 15 (chr15:53338796A>G, p = 1.5×10-7). Haplotype analysis and fine-mapping suggests that ILR7 and FBXW7, respectively, both important for regulation of immune system function, could be the underlying associated genes. Further evaluation of these regions and the previously identified DLA II locus across all three breeds, revealed an enrichment of nominal significant SNPs associated with chromosome 15 in pug dogs and DLA II in Maltese and Chihuahua dogs. Meta-analysis confirmed effect sizes the same direction in all three breeds for both the chromosome 15 and DLA II loci (p = 8.6×10-11 and p = 2.5×10-7, respectively). This suggests a shared genetic background exists between all breeds and confers susceptibility to NME, but effect sizes might be different among breeds. In conclusion, we identified the first genetic risk factors for NME development in the Maltese, chromosome 4 and chromosome 15, and provide evidence for a shared genetic risk between breeds associated with chromosome 15 and DLA II. Last, DLA II and IL7R both have been implicated in human inflammatory diseases of the central nervous system such as multiple sclerosis, suggesting that similar pharmacotherapeutic targets across species should be investigated.

Alaskan Husky Encephalopathy (AHE) has been previously proposed as a mitochondrial encephalopathy based on neuropathological similarities with human Leigh Syndrome (LS). We studied 11 Alaskan Husky dogs with AHE, but found no abnormalities in respiratory chain enzyme activities in muscle and liver, or mutations in mitochondrial or nuclear genes that cause LS in people. A genome wide association study was performed using eight of the affected dogs and 20 related but unaffected control AHs using the Illumina canine HD array. SLC19A3 was identified as a positional candidate gene. This gene controls the uptake of thiamine in the CNS via expression of the thiamine transporter protein THTR2. Dogs have two copies of this gene located within the candidate interval (SLC19A3.2 - 43.36-43.38 Mb and SLC19A3.1 - 43.411-43.419 Mb) on chromosome 25. Expression analysis in a normal dog revealed that one of the paralogs, SLC19A3.1, was expressed in the brain and spinal cord while the other was not. Subsequent exon sequencing of SLC19A3.1 revealed a 4bp insertion and SNP in the second exon that is predicted to result in a functional protein truncation of 279 amino acids (c.624 insTTGC, c.625 C>A). All dogs with AHE were homozygous for this mutation, 15/41 healthy AH control dogs were heterozygous carriers while 26/41 normal healthy AH dogs were wild type. Furthermore, this mutation was not detected in another 187 dogs of different breeds. These results suggest that this mutation in SLC19A3.1, encoding a thiamine transporter protein, plays a critical role in the pathogenesis of AHE.

Neural tube defects (NTDs) is a general term for central nervous system malformations secondary to a failure of closure or development of the neural tube. The resulting pathologies may involve the brain, spinal cord and/or vertebral column, in addition to associated structures such as soft tissue or skin. The condition is reported among the more common birth defects in humans, leading to significant infant morbidity and mortality. The etiology remains poorly understood but genetic, nutritional, environmental factors, or a combination of these, are known to play a role in the development of NTDs. The variable conditions associated with NTDs occur naturally in dogs, and have been previously reported in the Weimaraner breed. Taking advantage of the strong linkage-disequilibrium within dog breeds we performed genome-wide association analysis and mapped a genomic region for spinal dysraphism, a presumed NTD, using 4 affected and 96 unaffected Weimaraners. The associated region on canine chromosome 8 (pgenome  =3.0 × 10(-5)), after 100,000 permutations, encodes 18 genes, including NKX2-8, a homeobox gene which is expressed in the developing neural tube. Sequencing NKX2-8 in affected Weimaraners revealed a G to AA frameshift mutation within exon 2 of the gene, resulting in a premature stop codon that is predicted to produce a truncated protein. The exons of NKX2-8 were sequenced in human patients with spina bifida and rare variants (rs61755040 and rs10135525) were found to be significantly over-represented (p=0.036). This is the first documentation of a potential role for NKX2-8 in the etiology of NTDs, made possible by investigating the molecular basis of naturally occurring mutations in dogs., Competing Interests: The authors have declared that no competing interests exist.

Objective: To identify matrix metalloproteinase (MMP)-2 and -9 in CSF from dogs with intracranial tumors., Sample: CSF from 55 dogs with intracranial tumors and 37 control dogs., Procedures: Latent and active MMP-2 and -9 were identified by use of gelatin zymography. The presence of MMPs in the CSF of dogs with intracranial tumors was compared with control dogs that were clinically normal and with dogs that had idiopathic or cryptogenic epilepsy or peripheral vestibular disease. Relationships between MMP-9 and CSF cell counts and protein were also investigated., Results: Latent MMP-2 was found in CSF samples from all dogs, although active MMP-2 was not detected in any sample. Latent MMP-9 was detected in a subset of dogs with histologically documented intracranial tumors, including meningiomas (2/10), gliomas (3/10), pituitary tumors (1/2), choroid plexus tumors (5/6), and lymphoma (4/4), but was not detected in any control samples. Dogs with tumors were significantly more likely than those without to have detectable MMP-9 in the CSF, and the presence of MMP-9 was associated with higher CSF nucleated cell counts and protein concentration., Conclusions and Clinical Relevance: Latent MMP-9 was detected in most dogs with choroid plexus tumors or lymphoma but in a smaller percentage of dogs with meningiomas, gliomas, or pituitary tumors. Detection of MMP in CSF may prove useful as a marker of intracranial neoplasia or possibly to monitor response of tumors to therapeutic intervention.

Background: Cryptococcus spp. is a fungal pathogen with a predilection for the central nervous system (CNS)., Objectives: To compare the clinical, advanced imaging, and neuropathologic findings in dogs and cats with CNS cryptococcosis, and to evaluate outcome of treatment in these animals., Animals: Twenty-six cats and 21 dogs with CNS cryptococcosis., Methods: Medical records were reviewed for clinical findings and results of CNS imaging. Archived cerebrospinal fluid and CNS tissue specimens were reviewed for pathology. Findings in cats were compared with those in dogs and the effects of variables on survival were determined by survival curve analysis., Results: When present, pain was localized to the cervical region in dogs and was generalized or localized to the thoracolumbar spine or pelvic limbs in cats. Magnetic resonance imaging (MRI) findings were variable but correlated with CNS histopathological findings of meningitis, meningitis with gelatinous pseudocyst formation, and granulomatous mass lesions. Peripherally enhancing brain lesions were seen only in cats. Histopathologically, the inflammatory response was milder in cats compared with dogs. Remissions of ≥1 year occurred in 32% of treated animals. Altered mentation was associated with negative outcome. Glucocorticoid use after diagnosis was associated with improved survival in the first 10 days., Conclusions and Clinical Importance: Lesions seen on MRI reflected neuropathological findings and were similar to those reported in human patients. The immune response to infection may differ between cats and dogs, or relate to the infecting cryptococcal species. Long-term (>6 month median survival time) survival may be possible in animals surviving ≥4 days after diagnosis., (Copyright © 2010 by the American College of Veterinary Internal Medicine.)

Background: Marked eosinophilic meningitis or meningoencephalomyelitis (EME) is rarely reported in dogs and the cause is usually undetermined. Long-term prognosis for dogs with cerebrospinal fluid (CSF) eosinophilia is variable., Animals: Twenty-three client-owned dogs., Methods: Retrospective case series. Dogs with eosinophilic CSF, defined as total nucleated cell count (TNCC) >3 cells/microL with >20% eosinophils, were identified by a computerized search of all dogs having cisternal and/or lumbar CSF analyzed as part of the diagnostic workup between 1992 and 2007., Results: TNCC in CSF ranged from 4 to 4,740 cells/microL (median 84 cells/microL, reference range

Background: Choroid plexus tumors (CPTs) comprise approximately 10% of all primary brain tumors in dogs. The clinical utility of magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, or both in the presumptive diagnosis of CPTs has not been determined., Objectives: To report MRI and CSF findings in dogs with CPT and determine if there are distinguishing features that allow clinical discrimination between the tumor grades., Animals: Fifty-six client-owned dogs with naturally occurring CPT., Methods: Retrospective case series. The inclusion criterion was histologically confirmed CPT. Blinded review of cranial MRI and cisternal CSF analysis was performed., Results: Thirty-six of 56 dogs had a choroid plexus carcinoma (CPC) and 20 had a choroid plexus papilloma (CPP). Golden Retrievers were overrepresented compared with the hospital population (frequency 3.7 times that expected, confidence interval 95%= 2.0-6.7, P< .0002). Median CSF protein concentration in CPCs (108 mg/dL, range 27-380 mg/dL) was significantly higher than in CPPs (34 mg/dL, range 32-80 mg/dL) (P= .002). Only dogs with CPCs had a CSF protein concentration >80 mg/dL. Cytological evidence of malignancy in CSF was seen in 7 of 15 CPCs. Only CPCs had evidence of intraventricular or subarachnoid metastases on MRI., Conclusions and Clinical Importance: MRI, CSF analysis or both can help to differentiate between CPPs and CPCs, and may provide valuable prognostic and pretreatment information.

Case Description: 2 dogs (dogs 1 and 2) were examined for sudden onset of blindness. Both dogs had mild obtundation and mydriasis in both eyes. It was thought that dog 1 may have ingested ivermectin; dog 2 had been treated with ivermectin for demodectic mange., Clinical Findings: On initial examination, both dogs had mydriasis and decreased pupillary light reflexes in both eyes. Dog 1 had an absent menace response bilaterally. Fundic examination of both eyes in both dogs revealed regions of multifocal retinal edema and folds with low-lying retinal separation. The electroretinogram was extinguished in dog 1 and attenuated in dog 2. Ivermectin was detected in serum samples from both dogs., Treatment and Outcome: Both dogs made a complete clinical recovery following cessation of exposure to ivermectin; electroretinographic findings improved, and retinal edema resolved with some residual chorioretinal scarring., Clinical Relevance: To our knowledge, this is the first report of resolution of retinal edema and electroretinographic changes associated with ivermectin toxicosis in dogs. In dogs that develop blindness suddenly, fundic examination, electroretinography, and assessment of serum ivermectin concentration are diagnostically useful, even if exposure to ivermectin is unknown.

Background: Cerebrospinal fluid (CSF) in dogs with Hansen type I intervertebral disc herniation (IVDH) is classically described as normal or mildly inflammatory with a predominance of large mononuclear cells or neutrophils in severe acute herniations. However, we have observed a moderate to marked pleocytosis with a predominance of lymphocytes in some dogs with IVDH., Hypothesis: Moderate to marked CSF pleocytosis occurs more commonly in dogs with type I IVDH than is reported in the literature. Lymphocytic predominance is more common than nonlymphocytic pleocytosis in dogs with chronic IVDH., Animals: Four hundred twenty-three client-owned dogs with type I IVDH., Methods: Retrospective study. Lumbar CSF of dogs with surgically confirmed type I IVDH was evaluated cytologically. Information obtained from medical records included signalment, prior clinical history, time from onset of signs to presentation, neurologic status, and intraoperative findings. Dogs with prior history and/or intraoperative evidence consistent with chronic IVDH before an acute herniation were termed acute-on-chronic (AOC)., Results: Pleocytosis (> 5 cells/uL) was present in 51% of dogs, including 23% with cervical IVDH and 61% with thoracolumbar IVDH. Moderate or marked inflammation (> or = 20 cells/uL) was identified in the CSF of 51% of dogs with thoracolumbar IVDH and pleocytosis. A predominance of lymphocytes was significantly more common in dogs examined > 7 days from onset of signs (P= .032) and in dogs with AOC IVDH (P= .0013)., Conclusions and Clinical Importance: Moderate to marked CSF pleocytosis in dogs with type I IVDH is more common than previously reported. Lymphocytic pleocytosis is most common in dogs with chronic progression or AOC IVDH. Lymphocytic inflammation in the CSF of some dogs might suggest an immune-mediated response to chronically herniated disc material.

Background: Meningioma is the most common primary intraspinal nervous system tumor in dogs. Clinical findings, clinicopathologic data, and treatment of these tumors have been reported sporadically, but little information is available regarding cerebrospinal fluid (CSF) analysis, histologic tumor grade, or efficacy of radiation therapy as an adjunct to cytoreductive surgery., Animals: Dogs with histologically confirmed intraspinal meningiomas (n = 34)., Methods: A retrospective study of dogs with intraspinal meningiomas between 1984 and 2006 was carried out. Signalment, historical information, physical examination, clinicopathologic data, radiation therapy protocols, surgery reports, and all available images were reviewed. All tumors were histologically classified and graded as defined by the international World Health Organization classification scheme for central nervous system tumors., Results: Intraspinal mengiomas in dogs are most common in the cervical spinal cord but can be found throughout the neuraxis. Location is correlated with histologic grade, with grade I tumors more likely to be in the cervical region than grade II tumors. Myelography generally shows an intradural extramedullary compressive lesion. On magnetic resonance imaging, the masses are strongly and uniformly contrast enhancing and a dural tail often is present. CSF analysis usually shows increased protein concentration with mild to moderate mixed pleocytosis. Surgical resection is an effective means of improving neurologic status, and adjunctive radiation therapy may lead to an improved outcome., Conclusions and Clinical Importance: Biopsy is necessary for definitive diagnosis, but imaging and CSF analysis can suggest a diagnosis of meningioma. Treatment of meningiomas with surgery and radiation therapy can result in a fair to excellent prognosis.

An acute to chronic idiopathic necrotizing meningoencephalitis was diagnosed in 5 Chihuahua dogs aged between 1.5 and 10 years. Presenting neurologic signs included seizures, blindness, mentation changes, and postural deficits occurring from 5 days to 5.5 months prior to presentation. Cerebrospinal fluid analyses from 2 of 3 dogs sampled were consistent with an inflammatory disease. Magnetic resonance imaging of the brain of 2 dogs demonstrated multifocal loss or collapse of cortical gray/white matter demarcation hypointense on T1-weighted images, with T2-weighted hyperintensity and slight postcontrast enhancement. Multifocal asymmetrical areas of necrosis or collapse in both gray and white matter of the cerebral hemispheres was seen grossly in 4 brains. Microscopically in all dogs, there was a severe, asymmetrical, intensely cellular, nonsuppurative meningoencephalitis usually with cystic necrosis in subcortical white matter. There were no lesions in the mesencephalon or metencephalon except in 1 dog. Immunophenotyping defined populations of CD3, CD11d, CD18, CD20, CD45, CD45 RA, and CD79a immunoreactive inflammatory cells varying in density and location but common to acute and chronic lesions. In fresh frozen lesions, both CD1b,c and CD11c immunoreactive dendritic antigen-presenting cells were also identified. Immunoreactivity for canine distemper viral (CDV) antigen was negative in all dogs. The clinical signs, distribution pattern, and histologic type of lesions bear close similarities to necrotizing meningoencephalitis as described in series of both Pug and Maltese breed dogs and less commonly in other breeds.

Background: Intracranial meningiomas are the most common primary brain tumors in dogs. Classification of meningiomas by tumor grade and subtype has not been reported, and the value of magnetic resonance imaging (MRI) characteristics for predicting tumor subtype and grade has not been investigated., Hypothesis: Canine intracranial meningiomas are a heterogenous group of tumors with differing histological subtypes and grades. Prediction of histopathological classification is possible based on MRI characteristics., Animals: One hundred and twelve dogs with a histological diagnosis of intracranial meningioma., Methods: Retrospective observational study., Results: Meningiomas were overrepresented in the Golden Retriever and Boxer breeds with no sex predilection. The incidence of specific tumor grades was 56% benign (Grade I), 43% atypical (Grade II), and 1% malignant (Grade III). Grade I histological subtypes included meningothelial (43%), transitional (40%), microcystic (8%), psammomatous (6%), and angiomatous (3%). No statistically significant (P < .05) associations were found among tumor subtype or grade and any of the MRI features studied., Conclusions and Clinical Importance: Meningiomas in dogs differ from their counterparts in humans mainly in their higher incidence of atypical (Grade II) tumors observed. MRI characteristics do not allow for prediction of meningioma subtype or grade, emphasizing the necessity of histopathology for antemortem diagnosis. The higher incidence of atypical tumors in dogs may contribute to the poorer therapeutic response in dogs with meningiomas as compared with the response in humans with meningiomas.

Brainstem dysfunction resulting from central extension of infection is a life-threatening complication of otitis media/interna (OMI) that has been described infrequently in dogs and cats. We review the clinical signs of disease, diagnostic findings, and results of surgical and medical treatments of brainstem disease attributable to otogenic intracranial infection in cats and dogs. Eleven cats and 4 dogs were examined because of acute, subacute, or chronic clinical signs of brain disease including central vestibular signs, altered mentation, abnormal posture/gait, cranial nerve deficits, and seizures. Results of a minimal database (CBC, serum biochemical panel, urinalysis, thoracic radiographs, and abdominal ultrasonographic images or radiographs) were within reference intervals in all animals. Magnetic resonance (MR) images of the head were acquired for all animals, and cisternal cerebrospinal fluid (CSF) from 9 of 11 cats and 3 of 4 dogs was examined. Surgical exploration and ventral bulla osteotomy were done for 12 of 15 animals, followed by 1-3 months of antibiotic therapy; the remaining animals were euthanized before treatment. In all animals, MR imaging was effective in characterizing the location and extent of the pathologic changes intracranially as well as within middle/inner ear structures. Results of CSF analysis were characteristic of bacterial infection in most of the animals with acute or subacute disease. Since long-term outcome in all treated animals was very good to excellent, it was concluded that dogs and cats with intracranial disease secondary to extension of otitis media/interna have a good-to-excellent prognosis when the condition was diagnosed and was treated by surgical exploration and appropriate antibiotic therapy.

Spinal cord dysfunction secondary to spinal arachnoid cysts (SACs) has been reported previously in dogs. This retrospective study reviews the clinical signs, radiographic findings, and outcome after surgical resection of SACs in 14 dogs. Plain vertebral column radiographs and myelography were done in all dogs. Computed tomography (CT) was done in 7 dogs and magnetic resonance (MR) imaging in 3 dogs. Affected dogs were between 1 and 12 years of age, and 8 of 14 were Rottweilers. Abnormalities detected on neurological examination depended on the location of the SAC. Five dogs had bilobed or multiple SACs. SACs were located in the cervical vertebral column in 11 dogs and in the thoracic vertebral column in 4 dogs. All dogs had dorsally or dorsolaterally located SACs. Two dogs also had additional ventrally located SACs. Spinal cord compression secondary to intervertebral disc extrusion or protrusion was demonstrated at the site of the SACs in 2 dogs. Surgical resection of the SACs was completed in all dogs. Eleven dogs were available for follow-up. Five weeks postoperatively, 7 dogs improved in neurological function, with some residual ataxia and paresis in 6 of these dogs. Neurological function had deteriorated in 4 dogs. It was concluded from this study that Rottweilers have a higher incidence of SACs than other breeds of dog. Furthermore, bilobed or multiple SACs can occur commonly, and myelography effectively localized SACs in dogs. Surgical resection of SACs resulted in improvement in neurological function in the majority of treated dogs.

Although pure granular cell tumors have been reported in various sites in the dog, only one tumor has been reported in the central nervous system. Two dogs presented with neurologic signs had brain lesions detected by magnetic resonance imaging in the area of the olfactory bulbs and frontal cortex. In both dogs, a clinical diagnosis of a granular cell tumor was made from tissues obtained from stereotactic biopsies guided by computed tomography. Surgical removal of the tumors was followed by histopathologic, ultrastructural, and immunocytochemical characterization. Although not conclusive, these studies indicated that the granular cells were not of leucocyte origin but may have been derived from the meninges. One dog died 12 months after surgery, and the other was alive 4 months later.

The recent application of neuroimaging techniques in veterinary neurology has led to the accurate localization of many types of intracranial lesions but has also created a clinical need, particularly with brain tumors, for a specific intraoperative diagnosis. For human brain tumors, a smear technique has been used successfully for many years to provide an extremely rapid, highly accurate intraoperative diagnosis. In similar smear preparations of intracranial lesions, obtained either by computed tomography (CT)-guided stereobiopsy or from a craniotomy, we have described distinguishing cytologic features of some primary spontaneous nervous system tumors in 80 dogs and 13 cats. A final diagnosis was confirmed by evaluation of paraffin-embedded sections from the same sample and, when appropriate, by immunocytochemical staining. Preliminary findings indicate that, in dogs and cats, this procedure is useful for rapid, accurate intraoperative diagnosis of many primary nervous system tumors. The distinguishing features of the canine and feline tumors bear a remarkably close resemblance to their human counterparts.

An understanding of the anatomy of the feline vestibular system is essential for interpretation of the clinical signs associated with vestibular dysfunction, for precise lesion localisation, and for accurate interpretation of results of diagnostic imaging. Appropriate recognition and interpretation of the clinical signs of vestibular disease is also an essential aspect of the precise diagnosis of the cause of vestibular dysfunction in cats. The objectives of this review are to provide an overview of the anatomy of the feline vestibular system, and to review the clinical signs of peripheral and central vestibular dysfunction of cats., (Copyright 1999 W.B. Saunders Company Ltd.)

An 8-year-old rabbit was referred to an ophthalmologist because of intermittent bilateral exophthalmos and prolapse of the nictitating membranes. Both eyes could be retropulsed normally, and the exophthalmos was induced with ventroflexion. The rabbit had moderate hypercalcemia and a large mediastinal mass that could be seen on thoracic radiographs. The rabbit's condition was unchanged for 5 months. It was reexamined because of weight loss and paroxysmal coughing and, at that time, was thin and tachypneic, and had reduced thoracic compliance. Thoracotomy was performed, and a 5-cm-diameter encapsulated mass, subsequently determined histologically to be thymoma, was removed. The rabbit was euthanatized after surgery because of complications. The periodic exophthalmos and hypercalcemia in this rabbit were believed to be paraneoplastic syndromes.