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Case summary A rescue charity-owned 6-month-old neutered female domestic shorthair cat was presented with progressive tetraparesis, increased extensor muscle tone and signs of spinocerebellar ataxia, including hypermetria. The cat’s male sibling, with similar progressive neurological signs, had been euthanased 2 months previously. An inherited metabolic disorder was suspected. Urine for determination of organic acid concentration was obtained and the cat was prescribed carnitine and taurine supplementation. The cat was euthanased 3 months later following progressive neurological signs, including ataxia, tetraparesis, tendency to fall, bilateral absent menace response and intention tremor. A selective post-mortem examination was obtained, taking samples from the brain, cervical spinal cord, tibial branch of the sciatic nerve, muscle, liver and kidneys. Organic acid analysis results received after euthanasia revealed a marked elevation of 3-hydroxy-3-methylglutaric acid (45 mmol/mol creatine [normal range 0–2]) and isovalerylglycine (27 mmol/mol creatinine [normal range 0–2]). 3-Hydroxy-3-methylglutaric acid was deemed clinically relevant as it is a metabolite of 3-hydroxy-3-methylglutaryl-CoA lyase, the enzyme involved in the final step of leucine degradation. Post-mortem examination revealed diffuse, chronic-active, severe olivoponto-(spino)-cerebellar degeneration. Relevance and novel information This is the first report of 3-hydroxy-3-methylglutaric aciduria in the veterinary literature and the first description of the neuropathology of this disorder in any species. 3-Hydroxy-3-methylglutaric aciduria in humans occurs rarely and is due to a deficiency in 3-hydroxy-3-methylglutaryl-coenzyme A lyase.

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.

Little is known about the importance of the vibrissae in domestic dogs and no studies have been published to date. The shaving of the vibrissae is still common in dogs, particularly in preparation for dog shows. In this publication, we show how dogs use their vibrissae with 17 video clips from 11 individuals. We also performed histological, transmission electron microscopic and immunohistochemical analyses to characterise the histomorphology of canine follicle-sinus complex (FSC). Tissue samples were taken from six dog carcasses. The videos show that dogs respond to mechanical stimulation of their vibrissae. Touching the superciliary and mystacial vibrissae induces a reflex blinking of the eyelids. Dogs also move their mystacial vibrissae forward to explore objects. Histomorphological and ultrastructural analyses confirmed that canine mystacial FSCs have the typical general histomorphology of mammalian sinusoidal vibrissae with dense innervation and specific mechanoreceptor structures. The follicles of the small hairs on the upper lip also have the typical canine FSC structure and, therefore, can be identified as ‘microvibrissae’. In conclusion, there is sufficient evidence to suggest that the vibrissae of the domestic dog are a functional sensory organ and should not be shaved for cosmetic reasons to protect the physical integrity of the dog.

Background Canine leishmaniosis (CanL), a sand fly-borne zoonotic disease caused by Leishmania infantum , is potentially lethal in dogs. A similar or slightly higher quantity of antigens over antibodies promotes the formation of soluble circulating immune complexes (sCIC), which are deposited in the capillary wall, causing the inflammatory cascade responsible for clinical manifestations. Nervous system involvement during CanL is rarely reported in both humans and dogs, and the exact underlying process involving the peripheral nervous system (PNS) is still debated in both species. Methods Two male mixed-breed dogs were presented for exercise intolerance, non-ambulatory flaccid tetraparesis and decreased/absent flexor reflexes in all four limbs. Both dogs were seropositive for L. infantum and presented clinicopathological abnormalities suggestive of active CanL. One dog had received N -methyl-glucamine antimoniate two months before presentation without neurological improvement. Results Generalized PNS involvement was confirmed in both dogs. Biopsies of muscle and nerve tissues showed mononuclear cell inflammatory infiltration, and quantitative real-time polymerase chain reaction (PCR) was positive for Leishmania spp. In addition, Leishmania spp. antigen was detected in the nerve from one dog by immunohistochemistry. Both dogs were started on N -methyl-glucamine antimoniate and allopurinol in association with immunosuppressive corticosteroid therapy, recovering in few weeks. Conclusions Peripheral neuropathies during active CanL can be a consequence of sCIC deposition on endoneurial vascular endothelium comprising the blood–nerve barrier and its consequent breakdown. However, an abnormal host immune response triggered by L. infantum causing demyelination and/or axonal disruption is also possible. The positive response to the immunosuppressive therapy further supports an immune-mediated origin of the PNS condition. Therefore, CanL should be included in the differential diagnosis of PNS disease in dogs, especially in areas endemic for L. infantum . Graphical Abstract

Feline infectious peritonitis (FIP) is caused by infection with the feline coronavirus (FCoV) and is fatal if left untreated. In most cats, FCoV primarily infects the gastrointestinal tract and remains asymptomatic or causes only mild enteritis, with only a small proportion of infected cats developing FIP. An excessive and harmful immune response leading to characteristic (pyo)granulomatous phlebitis is believed to play a key role in the development of FIP, along with complex interactions between host and viral factors. Our research group recently demonstrated successful treatment of cats with naturally occurring FIP using the antiviral nucleoside analogue GS-441524. Treatment led to complete recovery without any relapses for a follow-up period of one year, demonstrating both a short- and long-term cure. To investigate differential gene expression and corresponding molecular pathways in cats with FIP before, during, and after antiviral treatment, RNA sequencing was performed on full blood samples of 18 cats treated successfully in a prospective study. Samples were analyzed before treatment, at different timepoints while on treatment with GS-441524 and after completion of treatment. Additionally, gene expression profiles were compared to 12 healthy FCoV-infected control cats and 5 healthy uninfected control cats. The results revealed both a widespread dysregulation of the blood RNA signature in cats with FIP as well as its rapid normalization within the first week of treatment. Significant changes were already apparent within the first two days of treatment. The results of the present study suggest that elimination of the virus from the blood leads to rapid control and subsequent normalization of the damaging immune response, a finding that corresponds well to the clinical response to treatment. This study illustrates the host response to treatment at the molecular level and provides further evidence that a shorter treatment duration than the 84 days predominantly practiced is sufficient.

Borna disease virus 1 (BoDV-1) has long been recognized as a cause of fatal encephalitis in animals and was only recently identified as a zoonotic pathogen causing a similar disease in humans. This study provides the first comprehensive comparative analysis of BoDV-1-induced neuropathology in human and animal end hosts, including horses, sheep, and alpacas. Using immunohistochemical analyses, we investigated the topographical distribution of BoDV-1 and inflammatory responses in the central nervous system across 19 cases. Key findings reveal distinct differences and overlaps between humans and animals. While humans exhibited heterogeneous patterns especially of the lymphocyte infiltration, animals displayed more species-specific inflammation and viral spread patterns. In horses, the hippocampus and basal ganglia were consistently affected, whereas sheep showed predominant involvement of the frontal cortex and stria olfactoria. Alpacas demonstrated a less uniform distribution but highlighted the brainstem and basal ganglia as critical sites. Intriguingly, across all species, a negative association was observed between lymphocyte infiltration and the number of BoDV-1-infected cells. These findings enhance our understanding of BoDV-1 pathogenesis and is a first step of cross-species comparison in unraveling disease mechanisms in BoDV-1 infection. Further research is warranted to elucidate the implications of these findings for therapeutic strategies and to explore the entry and dissemination routes of BoDV-1 in different hosts.

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a common dis-ease in cats, fatal if untreated, and no effective treatment is currently legally available. The aim of this study was to evaluate efficacy and toxicity of the multi-component drug Xraphconn® in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects. Mass spectrometry and nuclear magnetic resonance identified GS-441524 as an active component of Xraphconn®. Eighteen cats with FIP were prospectively followed up while being treated orally for 84 days. Values of key parameters on each examination day were compared to values before treatment initiation using linear mixed-effect models. Xraphconn® displayed high virucidal activity in cell culture. All cats recovered with dramatic improvement of clinical and laboratory parameters and massive reduction in viral loads within the first few days of treatment without serious adverse effects. Oral treatment with Xraphconn® containing GS-441524 was highly effective for FIP without causing serious adverse effects. This drug is an excellent option for the oral treatment of FIP and should be trialed as potential effective treatment option for other severe coronavirus-associated diseases across species.

The nucleoside analogue GS-441524 is a common treatment for cats with feline infectious peritonitis (FIP). In a previous study, 40 cats with FIP with effusion were treated with 15 mg/kg GS-441524 orally once daily for either 42 days or 84 days, and a 42-day treatment was as effective as the earlier recommended 84-day treatment. The aim of the present study was to describe unexpected clinical and laboratory observations occurring during and after treatment (within one year) in these cats and to compare them regarding the different treatment durations. Thirty-eight cats recovered rapidly during treatment, two cats had to be euthanized, and one cat was lost to follow-up. During treatment, 25 cats developed diarrhea. Lymphocytosis occurred in 26/40 cats during treatment, eosinophilia in 25/40 during treatment, increased alanine aminotransferase activity in 22/40, alkaline phosphatase activity in 7/40, and symmetric dimethylarginine levels in 25/40. These unexpected observations occurred equally in both treatment duration groups, but statistically significantly more cats developed lymphocytosis and eosinophilia when treated for 84 days. Although most of the unexpected observations during GS-441524 treatment improved or disappeared after treatment termination, these conditions have to be monitored, and treatment should not be given for longer than necessary.

‘Staggering disease’ is a neurological disease entity considered a threat to European domestic cats ( Felis catus ) for almost five decades. However, its aetiology has remained obscure. Rustrela virus (RusV), a relative of rubella virus, has recently been shown to be associated with encephalitis in a broad range of mammalian hosts. Here, we report the detection of RusV RNA and antigen by metagenomic sequencing, RT-qPCR, in-situ hybridization and immunohistochemistry in brain tissues of 27 out of 29 cats with non-suppurative meningoencephalomyelitis and clinical signs compatible with’staggering disease’ from Sweden, Austria, and Germany, but not in non-affected control cats. Screening of possible reservoir hosts in Sweden revealed RusV infection in wood mice ( Apodemus sylvaticus ). Our work indicates that RusV is the long-sought cause of feline ‘staggering disease’. Given its reported broad host spectrum and considerable geographic range, RusV may be the aetiological agent of neuropathologies in further mammals, possibly even including humans. Rustrela virus (RusV) was detected in the brains of 27 out of 29 domestic cats with ‘staggering disease’, but not of 29 control cats. This suggests RusV as the long-sought causative agent of ‘staggering disease’, which had been obscure for 50 years.

Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, “a common language”, for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies. In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders.