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During excavations in 1929, a well-preserved skeleton was discovered in a sarcophagus in the Octagon at Ephesos (Turkey). For the following century, archaeologists have speculated about the identity of this obviously notable person. Repeated claim is that the remains could represent Arsinoë IV, daughter of Ptolemy XII, and younger (half-)sister of Cleopatra VII. To address these questions we undertook state-of-the-art morphological, genetic and dating analyses of the cranium and further analyses of bone samples from a femur and a rib of the skeleton found in the same tomb. We confirm based on genetic analyses from the cranium and the femur that they derive from the same person. 14 C-dating of the cranium provides a most likely time range between 205-36 BC. The connection with Arsinoë IV can be excluded because we confirmed that the individual is a male. The cranium represents an 11-14-year-old boy who suffered from significant developmental disturbances. Genetics suggest an ancestry from the Italian peninsula or Sardinia. The fate of the body of Arsinoë IV, who reportedly was killed in 41 BC in Ephesos, remains open. In contrast, investigations regarding the fate and social background of the boy from the Octagon can now proceed free of speculation., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Borna disease, which is a severe encephalitis that primarily affects horses and sheep, has been recognised for over two centuries. Borna disease virus 1 (BoDV-1) has been identified as a cause of a predominantly fatal encephalitis in humans. Little scientific data exist regarding the virus' transmission, entry portal, and excretion routes. Lesional patterns, immunological responses, and pathogenetic mechanisms remain largely unexplored in both reservoir and dead-end hosts. This systematic review compiles current knowledge on these aspects and provides guidance for future research. PubMed, ScienceDirect, and EBSCO were searched for publications from Jan 1, 2000, to April 30, 2024. 823 records were found, of which 41 studies were included. This systematic review discusses BoDV-1 transmission, pathogenesis, histopathological changes, and immunology in both reservoir and dead-end hosts, with special regard for humans. The exact propagation mechanisms, entry portal, and viral spread within the CNS are not entirely clear in humans. Although more data exist in animals, much remains hypothetical. Future research should focus on identifying potential entry sites and viral spread in dead-end hosts, which could help to clarify the pathogenesis and lesion distribution in the CNS, thereby contributing to a better understanding of BoDV-1 infection in humans and parallels with animal infections., Competing Interests: Declaration of interests CH is part of the consortium on Zoonotic Bornavirus (ZooBoCo) and is funded by the Federal Ministry of Education and Research (01KI1722E and 01KI2005E). FL-S receives funding from the Deutsche Forschungsgemeinschaft (504757758), support from the Bavarian State Ministry of Health, Care, and Prevention (Zoonotic Bornavirus Focalpoint Bavaria [ZooBoFo]), and has received honorarium for a scientific presentation on bornavirus encephalitis at Ingolstadt Hospital (Ingolstadt, Germany). KM has received honorarium and travel support for a presentation at the ACVIM Forum 2024. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Neuronal ceroid lipofuscinosis (NCL) represents a heterogenous group of lysosomal storage diseases resulting in progressive neurodegeneration. We investigated two Small Swiss Hound littermates that showed progressive ataxia and loss of cognitive functions and vision starting around the age of 12 months. Both dogs had to be euthanized a few months after the onset of disease owing to the severity of their clinical signs. Pathological investigation of one affected dog revealed cerebral and cerebellar atrophy with cytoplasmic accumulation of autofluorescent material in degenerating neurons. The clinical signs in combination with the characteristic histopathology led to a tentative diagnosis of NCL. In the subsequent genetic investigation, the genome of one affected dog was sequenced. This revealed a duplication of 18 819 bp within the MFSD8 gene. The duplication breakpoints were located in intron 3 and exon 12 of the gene and were predicted to disrupt the reading frame. Both affected dogs carried the duplication in a homozygous state and there was perfect cosegregation of the genotypes with the phenotype in a large pedigree, consistent with autosomal recessive inheritance. MFSD8 loss-of-function variants are a known cause of NCL7 in human patients, dogs and other mammalian species. The existing knowledge on MFSD8 together with the experimental data strongly suggests that the identified intragenic MFSD8 duplication caused the disease in the Small Swiss Hounds. These results allow their diagnosis to be refined to NCL7 and enable genetic testing in the breed to avoid further unintentional carrier × carrier matings., (© 2024 The Author(s). Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.)

ABSTRACT Borna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies. ABBREVIATIONS: BoDV-1: Borna disease virus 1; BVE: bornavirus encephalitis; Cb: cerebellum; CNS: central nervous system; FL: frontal lobe; GFAP: glial fibrillary acid protein; Hc: hippocampus; Iba1: ionized calcium-binding adapter molecule 1; Iba1 act : general activation of microglial cells; Iba1 nod : formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; pat early : patients treated with early high dose steroid shot; pat late : patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum.

Feline infectious peritonitis (FIP) is a fatal disease in cats caused by infection with feline coronavirus (FCoV). Despite severe inflammatory changes, defense mechanisms fail to achieve virus clearance. Some studies focused on various immune evasion mechanisms, but none of these studies elucidated the inefficacy of the complement system, which is one major player in FIP-associated immune pathogenesis. This study aimed to investigate the involvement of complement-regulating factors (CRFs). CRFs help modulate the immune response and prevent host tissue damage. Archived tissue samples from 31 deceased, FIP-affected cats were evaluated using multiplex immunohistochemistry for the spatial expression of the complement-regulating factors CD46 and CD59 in association with FIP lesions and their colocalization with complement-activating factor C1q and membrane attack complex C9 in relation to the presence and proximity of FCoV-infected cells. The FIP lesions of all 31 cats exhibited marked expression of both complement-regulating factors in proximity to FCoV-infected macrophages. Moreover, their expression in all 31 animals was significantly lower than the expression of the complement-activating factors C1q and C9 compared to areas farther distal to FCoV-infected cells. In conclusion, FCoV-infected macrophages in cats with FIP appear to use autocrine and paracrine expression of complement-regulating factors in their immediate environment to shield themselves from destruction by the complement system.

Borna disease virus 1 (BoDV-1) is the causative agent of Borna disease, a fatal neurologic disorder of domestic mammals and humans, resulting from spill-over infection from its natural reservoir host, the bicolored white-toothed shrew (Crocidura leucodon). The known BoDV-1-endemic area is remarkably restricted to parts of Germany, Austria, Switzerland and Liechtenstein. To gain comprehensive data on its occurrence, we analysed diagnostic material from suspected BoDV-1-induced encephalitis cases based on clinical and/or histopathological diagnosis. BoDV-1 infection was confirmed by RT-qPCR in 207 domestic mammals, 28 humans and seven wild shrews. Thereby, this study markedly raises the number of published laboratory-confirmed human BoDV-1 infections and provides a first comprehensive summary. Generation of 136 new BoDV-1 genome sequences from animals and humans facilitated an in-depth phylogeographic analysis, allowing for the definition of risk areas for zoonotic BoDV-1 transmission and facilitating the assessment of geographical infection sources. Consistent with the low mobility of its reservoir host, BoDV-1 sequences showed a remarkable geographic association, with individual phylogenetic clades occupying distinct areas. The closest genetic relatives of most human-derived BoDV-1 sequences were located at distances of less than 40 km, indicating that spill-over transmission from the natural reservoir usually occurs in the patient´s home region., (© 2024. The Author(s).)

An 8-year-old mixed-breed dog was presented with cervical hyperesthesia, tetraparesis, and mild proprioceptive ataxia in all four limbs. 3 Tesla MRI showed a dorsal compressive intradural-extramedullary mass at the level of C1-C2, isointense to the gray matter with a hypointense ventral core on T2 weighted images (WI), isointense on T1WI, with a strong and homogeneous contrast enhancement. A C1-C2 partial dorsal laminectomy was performed, and the lesion was removed en bloc. The histopathological and immunohistochemical analysis defined the diagnosis of inflammatory pseudotumor., (© 2024 American College of Veterinary Radiology.)

Background: Early diagnosis of neosporosis in dogs is challenging., Objectives: To evaluate the feasibility of a compound multimodal testing approach for diagnosing in dogs neuromuscular and combined forms of neosporosis., Animals: A total of 16 dogs diagnosed with solely neuromuscular neosporosis or with a combination of neuromuscular and central nervous system neosporosis., Methods: Retrospective review of clinical signs, laboratory findings, treatment, and outcome with focus on the diagnostic utility of different tests. Development of a chromogenic in situ hybridization (ISH) assay for the identification of Neospora caninum in paraffin-embedded muscle samples., Results: 13/16 dogs had only neuromuscular signs of neosporosis, 3/16 had disease signs with concomitant central nervous system (CNS) involvement. Serology was performed in 15/16, with 10/15 showing titers >1 : 160 at admission. PCR on muscle samples detected N. caninum DNA in 11/16. Immunohistochemistry (IHC) detected N. caninum in 9/16 and ISH in 9/16. Histopathology revealed inflammatory myopathy in 10/16, necrotizing myopathy in 5/16, borderline changes in 1/16 and tachyzoites in 9/16. In 4 cases, N. caninum infection was confirmed with all 5 diagnostic methods, 3 cases with 4, 2 with 3, 6 with 2, and 1 animal with 1., Conclusions and Clinical Importance: Diagnosis of N. caninum infection should rely on a multimodal diagnostic approach and negativity of 1 single test should not allow for exclusion. Serology in combination with direct parasite identification via histopathology, DNA via PCR, or both modalities, appears a reliable diagnostic approach., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Earlier, we described a breed-specific inflammatory myopathy in Dutch Kooiker dogs (Het Nederlandse Kooikerhondje), one of the nine Dutch breeds. The disease commonly manifests itself with clinical signs of difficulty walking, muscle weakness, exercise intolerance, and/or dysphagia. In nearly all dogs' creatine kinase (CK) activity was elevated. Histopathology reveals the infiltration of inflammatory cells within the skeletal muscles. The objective of this study was to further investigate and characterize the histopathological changes in muscle tissue and immunophenotype the inflammatory infiltrates. FFPE fixed-muscle biopsies from 39 purebred Kooiker dogs were included and evaluated histopathologically according to a tailored classification scheme for skeletal muscle inflammation. As in other breed-related inflammatory myopathies, multifocal, mixed, and predominantly mononuclear cell infiltration was present, with an initial invasion of viable muscle fibres and the surrounding stroma leading to inflammation, necrosis, and tissue damage. Immunophenotyping primarily revealed lymphohistiocytic infiltrates, with CD3+ T-cells being the predominant inflammatory cell type, accompanied by CD8+ cytotoxic T-cells. The concurrent expression of MHC-II class molecules on myofibres suggests their involvement in initiating and maintaining inflammation. Additionally, CD20+ B-cells were identified, though in lower numbers compared to T-cells, and IBA-1-positive macrophages were frequently seen. These findings suggest a breed-specific subtype of polymyositis in Kooiker dogs, akin to other breeds. This study sheds light on the immune response activation, combining adaptive and innate mechanisms, contributing to our understanding of polymyositis in this breed.

An 8-year-old rabbit presented with a 5-day history of acute difficulty in walking. Neurological examination revealed tetraparesis, proprioceptive deficits in both pelvic limbs and the right thoracic limb, decreased withdrawal reflex on the right thoracic limb and hyperreflexia in the pelvic limbs. A cervico-thoracic (C6-T2) localization was suspected. Computer tomography (CT) and magnetic resonance imaging (MRI) scans were performed, revealing a right dorsolateral extradural lesion at the C6-C7 intervertebral disc space. Additionally, meningeal and paravertebral contrast enhancement was observed on MRI, while periosteal reaction was evident at the right C6-C7 facet joint on CT. The findings were primarily consistent with spinal cord compression due to the presence of extruded disc material. Following conservative treatment failure, a right-sided C6-C7 hemilaminectomy was performed to remove the compression and sample the extradural material. Histological examination confirmed the presence of degenerated and partially mineralized disc material mixed with granulation tissue. This is the first reported case of cervical disc extrusion in a rabbit, confirmed by histological examination.

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective., Competing Interests: The authors declare that they have no conflict of interest. The GS-441524 tablets were provided by BOVA Specials, London, UK, but BOVA played no role in the interpretation of study data or the decision to submit the manuscript for publication. No commercial conflict of interest exists as the information is solely for scientific dissemination.

This case report describes a 17-month-old Pudelpointer with recurring motor impairment localized to the left thoracic limb. A neurological exam highlighted lameness in that limb, accompanied by pre-scapular swelling. Radiographs and magnetic resonance imaging detected an osseous structure in soft tissues close to the fifth cervical vertebra, and subsequent surgery uncovered adjacent cervical spinal nerve impingement. Histology of the bony structure revealed heterotopic ossification in paravertebral muscles. Mild bone re-formation at the operating site was detected after a 2-year period, but the patient was asymptomatic. This article reports the first case of heterotopic ossification with spinal nerve entrapment in a dog and adds a new differential diagnosis to the causes of neurogenic lameness in dogs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hajek, Rosati, Matiasek, Babinsky, Caine and Palus.)

Background: Inflammatory demyelinating diseases of the central nervous system, such as multiple sclerosis, are significant sources of morbidity in young adults despite therapeutic advances. Current murine models of remyelination have limited applicability due to the low white matter content of their brains, which restricts the spatial resolution of diagnostic imaging. Large animal models might be more suitable but pose significant technological, ethical and logistical challenges., Methods: We induced targeted cerebral demyelinating lesions by serially repeated injections of lysophosphatidylcholine in the minipig brain. Lesions were amenable to follow-up using the same clinical imaging modalities (3T magnetic resonance imaging, 11 C-PIB positron emission tomography) and standard histopathology protocols as for human diagnostics (myelin, glia and neuronal cell markers), as well as electron microscopy (EM), to compare against biopsy data from two patients., Findings: We demonstrate controlled, clinically unapparent, reversible and multimodally trackable brain white matter demyelination in a large animal model. De-/remyelination dynamics were slower than reported for rodent models and paralleled by a degree of secondary axonal pathology. Regression modelling of ultrastructural parameters (g-ratio, axon thickness) predicted EM features of cerebral de- and remyelination in human data., Interpretation: We validated our minipig model of demyelinating brain diseases by employing human diagnostic tools and comparing it with biopsy data from patients with cerebral demyelination., Funding: This work was supported by the DFG under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198) and TRR 274/1 2020, 408885537 (projects B03 and Z01)., Competing Interests: Declaration of interests CS, SH, BL, EL and TL are part of Ergosurg GmbH, which developed and manufactured the navigation system, the trackable instruments and the robotic system. VMB has received consulting fees from Brainlab. IY has received grants from the German Federal Ministry of Education and Research (BMBF) and the German Research Foundation (DFG), consulting fees from ABX-CRO, Blue Earth Diagnostics and Pentixapharm, honoraria from Piramal, support for attending meeting from the Society of Nuclear Medicine and Molecular Imaging, the European Association of Nuclear Medicine, the Slovenian Neuroscience Association (SiNAPSA) and the International Brain Research Organization, and is a member of the Neuroimaging Committee, European Association of Nuclear Medicine, the Board of Directors, Brain Imaging Council, Society of Nuclear Medicine and Molecular Imaging as well as the Molecular Connectivity Working Group. JK has received consulting fees from Novartis, possesses stock options at Bonescreen GmbH and was supported by the European Research Council, the DFG and the BMBF. TM has received speaker fees from Novartis and Roche as well as travel support from Novartis. BH has received consulting fees from GLG Consulting, Sandoz and Polpharma, possesses issued patents for detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis, as well as genetic determinants of neutralizing antibodies to interferon, and has participated on Data Safety Monitoring and Advisory Boards for Novartis, Sandoz, Polpharma, Allergycare, TG Therapeutics and Biocon., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Peripheral nerve sheath tumors (PNSTs) are a group of neoplasms originating from Schwann cells or pluripotent cell of the neural crest. Therapeutic options and prognosis are influenced by their degree of malignancy and location., Hypothesis/objectives: Identify magnetic resonance imaging (MRI) features predictive of PNST histologic grade., Animals: Forty-four dogs with histopathological diagnosis of spinal PNSTs and previous MRI investigation., Methods: A multicenter retrospective study including cases with (a) histopathologic diagnosis of PNST and (b) MRI studies available for review. Histologic slides were reviewed and graded by a board-certified pathologist according to a modified French system (FNCLCC) for grading soft tissue sarcomas. The MRI studies were reviewed by 2 board-certified radiologists blinded to the grade of the tumor and the final decision on the imaging characteristics was reached by consensus. Relationships between tumor grade and histological and MRI findings were assessed using statistical analysis., Results: Forty-four cases met inclusion criteria; 16 patients were PNSTs Grade 1 (low-grade), 19 were PNSTs Grade 2 (medium-grade), and 9 were PNSTs Grade 3 (high-grade). Large volume (P = .03) and severe peripheral contrast enhancement (P = .04) were significantly associated with high tumor grade. Degree of muscle atrophy, heterogeneous signal and tumor growth into the vertebral canal were not associated with grade., Conclusions and Clinical Importance: Grade of malignancy was difficult to identify based on diagnostic imaging alone. However, some MRI features were predictive of high-grade PNSTs including tumor size and peripheral contrast enhancement., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

As evidenced by sero-epidemiological studies, infections of horses with the tick-borne encephalitis virus (TBEV) occur frequently in TBEV-endemic areas. However, there are only very few reports of clinical cases. A possible underreporting may be due to a variety of diagnostic challenges. In this study, ELISA and neutralization tests were applied to serum samples. Brain tissue samples were investigated for the presence of nucleic acids of TBEV, Equid alphaherpesvirus 1 , Borna disease virus 1, West Nile and Usutu viruses, rustrela virus, as well as Eastern, Western, and Venezuelan equine encephalitis viruses with RT-qPCR, RT-PCR, and qPCR, respectively. TBEV-specific amplification products were subjected to Sanger sequencing. In addition, a direct fluorescent antibody test for rabies was performed. Clinical and patho-histological findings are reported. Using specific RT-qPCR and RT-PCR assays, TBEV nucleic acids were demonstrated in brain tissue samples. Sequencing revealed the Western (formerly Central) European subtype of TBEV as the etiological agent. A high titer of TBEV-specific neutralizing antibodies was found in the serum. RNAscope in situ hybridization revealed TBEV RNA confined to neuronal cell bodies and processes. No other pathogens or nucleic acids thereof could be detected. Diagnostic procedures need to be carried out early after the onset of neurological signs to allow for a final etiological diagnosis of acute TBEV infections in horses.

Hereditary hyperekplexia is a rare neuronal disorder characterized by an exaggerated startle response to sudden tactile or acoustic stimuli. In this study, we present a Miniature Australian Shepherd family showing clinical signs, which have genetic and phenotypic similarities with human hereditary hyperekplexia: episodes of muscle stiffness that could occasionally be triggered by acoustic stimuli. Whole genome sequence data analysis of two affected dogs revealed a 36-bp deletion spanning the exon-intron boundary in the glycine receptor alpha 1 (GLRA1) gene. Further validation in pedigree samples and an additional cohort of 127 Miniature Australian Shepherds, 45 Miniature American Shepherds and 74 Australian Shepherds demonstrated complete segregation of the variant with the disease, according to an autosomal recessive inheritance pattern. The protein encoded by GLRA1 is a subunit of the glycine receptor, which mediates postsynaptic inhibition in the brain stem and spinal cord. The canine GLRA1 deletion is located in the signal peptide and is predicted to cause exon skipping and subsequent premature stop codon resulting in a significant defect in glycine signaling. Variants in GLRA1 are known to cause hereditary hyperekplexia in humans; however, this is the first study to associate a variant in canine GLRA1 with the disorder, establishing a spontaneous large animal disease model for the human condition., (© 2023. The Author(s).)

Objectives: Feline infectious peritonitis (FIP), a common disease in cats caused by feline coronavirus (FCoV), is usually fatal once clinical signs appear. Successful treatment of FIP with oral GS-441524 for 84 days was demonstrated recently by this research group. The aim of this study was to evaluate the long-term outcome in these cats., Methods: A total of 18 successfully treated cats were followed for up to 1 year after treatment initiation (9 months after completion of the antiviral treatment). Follow-up examinations were performed at 12-week intervals, including physical examination, haematology, serum biochemistry, abdominal and thoracic ultrasound, FCoV ribonucleic acid (RNA) loads in blood and faeces by reverse transciptase-quantitative PCR and anti-FCoV antibody titres by indirect immunofluorescence assay., Results: Follow-up data were available from 18 cats in week 24, from 15 cats in week 36 and from 14 cats in week 48 (after the start of treatment), respectively. Laboratory parameters remained stable after the end of the treatment, with undetectable blood viral loads (in all but one cat on one occasion). Recurrence of faecal FCoV shedding was detected in five cats. In four cats, an intermediate short-term rise in anti-FCoV antibody titres was detected. In total, 12 cats showed abdominal lymphadenomegaly during the follow-up period; four of them continuously during the treatment and follow-up period. Two cats developed mild neurological signs, compatible with feline hyperaesthesia syndrome, in weeks 36 and 48, respectively; however, FCoV RNA remained undetectable in blood and faeces, and no increase in anti-FCoV antibody titres was observed in these two cats, and the signs resolved., Conclusions and Relevance: Treatment with GS-441524 proved to be effective against FIP in both the short term as well as the long term, with no confirmed relapse during the 1-year follow-up period. Whether delayed neurological signs could be a long-term adverse effect of the treatment or associated with a 'long FIP syndrome' needs to be further evaluated.

Background: Autoimmune mechanisms represent a novel category for causes of seizures and epilepsies in humans, and LGI1-antibody associated limbic encephalitis occurs in cats., Hypothesis/objectives: To investigate the presence of neural antibodies in dogs with epilepsy or dyskinesia of unknown cause using human and murine assays modified for use in dogs., Animals: Fifty-eight dogs with epilepsy of unknown cause or suspected dyskinesia and 57 control dogs., Methods: Serum and CSF samples were collected prospectively as part of the diagnostic work-up. Clinical data including onset and seizure/episode type were retrieved from the medical records. Screening for neural antibodies was done with cell-based assays transfected with human genes for typical autoimmune encephalitis antigens and tissue-based immunofluorescence assays on mouse hippocampus slices in serum and CSF samples from affected dogs and controls. The commercial human und murine assays were modified with canine-specific secondary antibody. Positive controls were from human samples., Results: The commercial assays used in this study did not provide unequivocal evidence for presence of neural antibodies in dogs including one dog with histopathologically proven limbic encephalitis. Low titer IgLON5 antibodies were present in serum from one dog from the epilepsy/dyskinesia group and in one dog from the control group., Conclusion and Clinical Importance: Specific neural antibodies were not detected using mouse and human target antigens in dogs with epilepsy and dyskinesia of unknown origin. These findings emphasize the need for canine-specific assays and the importance of control groups., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

The Dutch Kooiker dog (het Nederlandse Kooikerhondje) is one of nine Dutch dog breeds. As of 1960, a number of heritable diseases have been noted in this breed. One is an inflammatory myopathy that emerged in 1972, with numbers of affected dogs gradually increasing during the last few decades. The objective of this paper is to describe clinical signs, laboratory results, electromyography and histopathology of the muscle biopsies of the affected dogs. Method: Both retrospectively as well as prospectively affected Kooiker dogs were identified and categorized using a Tiered level of Confidence. Results: In total, 160 Kooiker dogs-40 Tier I, 33 Tier II and 87 Tier III-were included. Clinical signs were (1) locomotory problems, such as inability to walk long distances, difficulty getting up, stiff gait, walking on eggshells; (2) dysphagia signs such as drooling, difficulty eating and/or drinking; or (3) combinations of locomotory and dysphagia signs. CK activities were elevated in all except for one dog. Histopathology revealed a predominant lymphohistiocytic myositis with a usually low and variable number of eosinophils, neutrophils and plasma cells. It is concluded that, within this breed, a most likely heritable inflammatory myopathy occurs. Further studies are needed to classify this inflammatory myopathy, discuss its treatment, and unravel the genetic cause of this disease to eradicate it from this population.

'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., (© 2023. The Author(s).)

Choroid plexus tumors are commonly described as intraventricular mass lesions and account for 7-10% of intracranial, primary tumors in dogs. A 3-year-old Shetland sheepdog was presented with a history of slowly progressive lethargy, vision impairment and cognitive deficits. On magnetic resonance imaging, a subdural fluid accumulation (SFA) overlying and compressing the left parietotemporal lobe as well as multifocal changes consisting of cyst-like lesions, supposed intra-axial brain lesions and mild, multifocal meningeal thickening and generalized contrast enhancement were identified. Cerebrospinal fluid (CSF) analysis showed a mononuclear pleocytosis with negative results for infectious agents. The dog was treated with prednisolone followed by burr hole craniotomy with puncture of the SFA, which macroscopically appeared to be CSF-like fluid. After initial improvement, the dog deteriorated despite continuation of prednisolone and cytarabine therapy and was euthanized four weeks after surgery. Histopathology was consistent with a disseminated, neuroinvasive choroid plexus carcinoma (CPC) that involved the entire neuroaxis including the meninges of the brain and spinal cord. Immunohistochemical examination showed a strong Kir7.1 and a heterogenous cytokeratin-immunoreactivity in neoplastic cells. In conclusion, a CPC should be considered as a possible cause of a SFA even in the absence of an intraventricular mass lesion.

Gluten-related disorders in humans comprise different entities, including coeliac disease. Patients typically have measurable titers of anti-gliadin IgG or IgA (AGAs) and anti-transglutaminase-2 IgA (TG2). In addition to intestinal symptoms, human patients often show various neurological complications. In dogs, the neurological manifestation is rarely reported. Here we describe the muscle and nerve biopsies of an 11-year-old, male Border Terrier presenting with lower motor neuron signs submitted for histological examination. Examination of the biopsies showed an oligofocal lymphohistiocytic and plasmocytic myositis and a diffuse neuropathy of mixed nodo-paranodal and demyelinating type. Suspecting a neuromuscular form of breed-related gluten hypersensitivity, measurements of AGAs and TG2 antibodies were performed. Both titers ranged above control values. Hence, a gluten-related neuromyopathy was diagnosed. A gluten-free diet was prescribed and a complete disappearance of clinical signs was observed. Gluten-related disorders should be considered as a differential diagnosis in dogs with intestinal and neuromuscular signs., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Masticatory muscle myositis (MMM) is the second most common inflammatory myopathy diagnosed in dogs, but it is rarely described in puppies. The disease is characterized by the production of autoantibodies against 2M myofibers contained in masticatory muscle, although the cause of this production is still unclear. The aim of the present case report was to describe the clinical presentation, diagnostic findings, treatment, and follow-up of an atypical case of chronic masticatory muscle myositis in a very young dog. A 5-month old Cavalier king Charles Spaniel (CKCS) was presented to the AniCura Istituto Veterinario Novara with a two weeks, progressive history of lethargy and difficulty in food prehension. Neurological examination revealed bilateral masticatory muscle atrophy, mandibular ptosis with the jaw kept open, inability to close the mouth without manual assistance, jaw pain, and bilateral reduction of palpebral reflex and menace reaction; vision was maintained. A myopathy was suspected. Computed tomography (CT), magnetic resonance imaging (MRI), enzyme-linked immunosorbent assay test for 2M antibodies, and histopathological examination of masticatory muscle biopsy confirmed the diagnosis of MMM. Glucocorticoids treatment was started and clinical signs promptly improved. To the authors' knowledge, this is the first case describing mandibular ptosis in a dog affected by chronic MMM, successfully managed with medical treatment and the first report describing the CT and MRI findings in a young CKCS affected by MMM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Di Tosto, Callegari, Matiasek, Lacava, Salvatore, Muñoz Declara, Betti and Tirrito.)

This is the first report on a clinical follow-up and postmortem examination of a cat that had been cured of feline infectious peritonitis (FIP) with ocular manifestation by successful treatment with an oral multicomponent drug containing GS-441524. The cat was 6 months old when clinical signs (recurrent fever, lethargy, lack of appetite, and fulminant anterior uveitis) appeared. FIP was diagnosed by ocular tissue immunohistochemistry after enucleation of the affected eye. The cat was a participant in a FIP treatment study, which was published recently. However, 240 days after leaving the clinic healthy, and 164 days after the end of the 84 days of treatment, the cured cat died in a road traffic accident. Upon full postmortem examination, including histopathology and immunohistochemistry, there were no residual FIP lesions observed apart from a generalized lymphadenopathy due to massive lymphoid hyperplasia. Neither feline coronavirus (FCoV) RNA nor FCoV antigen were identified by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry, respectively, in any tissues or body fluids, including feces. These results prove that oral treatment with GS-441524 leads to the cure of FIP-associated changes and the elimination of FCoV from all tissues.

(1) Background: This study aimed to detect feline coronavirus (FCoV) and characterize spike (S) gene mutation profiles in cats suffering from diseases other than feline infectious peritonitis (FIP) using commercial real-time reverse transcription polymerase chain reaction (RT-qPCR) and reevaluating results by sequencing. (2) Methods: In 87 cats in which FIP was excluded by histopathology and immunohistochemistry, FCoV 7b gene and S gene mutation RT-qPCR was performed prospectively on incisional biopsies and fine-needle aspirates of different organs, body fluids, and feces. Samples positive for S gene mutations or mixed FCoV underwent sequencing. (3) Results: In 21/87 cats, FCoV RNA was detectable. S gene mutations were detected by commercial RT-qPCR (and a diagnostic algorithm that was used at the time of sample submission) in at least one sample in 14/21 cats (66.7%), with only mutated FCoV in 2/21, only mixed in 1/21, and different results in 11/21 cats; in the remaining 7/21 cats, RNA load was too low to differentiate. However, sequencing of 8 tissue samples and 8 fecal samples of 9 cats did not confirm mutated FCoV in any of the FCoV RNA-positive cats without FIP. (4) Conclusions: Sequencing results did not confirm results of the commercial S gene mutation RT-qPCR.

Three-dimensional (3D) printing techniques for patient-individual medicine has found its way into veterinary neurosurgery. Because of the high accuracy of 3D printed specific neurosurgical navigation devices, it seems to be a safe and reliable option to use patient-individual constructions for sampling brain tissue. Due to the complexity and vulnerability of the brain a particularly precise and safe procedure is required. In a recent cadaver study a better accuracy for the 3D printed MRI-based patient individual stereotactic brain biopsy device for dogs is determined compared to the accuracies of other biopsy systems which are currently used in veterinary medicine. This case report describes the clinical use of this 3D printed MRI-based patient individual brain biopsy device for brain sampling in three dogs. The system was characterized by a simple handling. Furthermore, it was an effective and reliable tool to gain diagnostic brain biopsy samples in dogs with no significant side effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gutmann, Flegel, Müller, Möbius, Matiasek, König, Winkler and Grunert.)