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Background: In dogs with idiopathic epilepsy (IE), 33% develop resistance to conventional anti-seizure medication (ASM) despite adequate treatment. In human medicine, an immune-mediated etiology is suspected in a subset of ASM-resistant patients with epilepsy and cerebrospinal fluid (CSF)-specific immunoglobulin G (IgG)-type oligoclonal bands (OCBs) have been detected. In dogs, cases of autoimmune encephalitis recently were reported. Neuroinflammation may provide an additional explanation for the lack of response of certain dogs with IE to ASM., Hypothesis: Cerebrospinal fluid-specific OCBs are found in a subgroup of dogs with ASM-resistant IE., Animals: Eighty-four dogs with IE were recruited from 3 referral centers and classified based on their response to ASM treatment (responsive, n = 56; resistant, n = 28)., Methods: Detection of OCBs was performed using isoelectric focusing (IEF) followed by immunoblotting. Associations of CSF-specific OCBs with seizure type, severity, and response to ASM were calculated using logistic regression models., Results: The overall frequency of CSF-specific OCBs in dogs with IE was 15.5% (95% confidence interval [CI], 8.5%-25%). In dogs with ASM-resistant IE, 21.4% (6/28) had CSF-specific OCBs compared with only 12.5% (7/56) in those responsive to ASM, but no evidence of an association was detected (odds ratio, 1.9; 95% CI, 0.57-6.35; P = .29)., Conclusions and Clinical Importance: Cerebrospinal fluid-specific OCBs were detected in a subgroup of dogs with IE. This finding could indicate that intrathecal IgG synthesis as a sign of neuroinflammation may play a role in disease pathogenesis., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objectives: Window entrapment in cats can lead to reduced blood flow to the spinal cord, muscles and nerves, resulting in ischaemic neuromyelomyopathy. The severity and duration of entrapment greatly influence clinical and neurological outcomes, as well as prognosis. The aim of the present retrospective multicentric study (2005-2022) was to describe clinical, neurological and selected clinicopathological findings, as well as the outcome of cats trapped in bottom-hung windows, presented to both first-opinion and referral-only clinics., Methods: The study included cats with detailed clinical and neurological evaluations at admission, along with at least one of the following biochemical parameters: creatine kinase (CK), aspartate transaminase (AST), alanine aminotransferase (ALT) activities, urea and/or creatinine. Clinical and neurological parameters evaluated in the study included rectal temperature, femoral pulse, gait, urinary bladder function, tail function and survival to discharge. Odds ratios (ORs) were calculated for survival and each clinical, neurological and biochemical variable., Results: Of the 70 cats that met the inclusion criteria, only seven (10%) died or were euthanased during hospitalisation. Nevertheless, with the available data, we found evidence of an association between clinical and neurological status and survival, with tail function being the strongest association. Cats lacking tail sensation, motor function and/or tonus were more likely to die than cats with normal tail function or only mild abnormalities (OR = 24). Similarly, cats with severe hypothermia or an absent femoral pulse were less likely to survive (OR = 12.75 and 7.5, respectively). In this sample (with a relatively low number of deaths), we did not find evidence of an association between CK, AST and ALT activity with survival. However, the only two cats with severe increases in creatinine died., Conclusions and Relevance: Assessment of gait, urinary bladder function, femoral pulse, rectal temperature and particularly tail function is promising for predicting outcomes in cats with window entrapment trauma., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Two female (FL 1, FL 2) and one male (ML) 11-wk-old, intact, captive African lion cubs ( Panthera leo leo ) were presented with a history of mild vestibular signs. Initial serum vitamin A concentrations were low (140 nmol/L) for ML. Calvarial hyperostosis was confirmed using computed tomography (CT) of the head and cervical vertebrae in each cub. CT measurements were adapted in relation to the skull width. ML showed the most pronounced thickening of the tentorium cerebelli and occipital bone, represented by a tentorium cerebelli to skull width ratio (TCR) of 0.08 (FL 1: 0.06, FL 2: 0.05) and a basisphenoid to skull width ratio (BBR) of 0.07 (FL 1: 0.06, FL 2: 0.04). Magnetic resonance imaging (MRI) revealed cerebellar herniation and cervical intramedullary T2-weighted hyperintensity from C1, extending caudally for at least two cervical vertebrae in all cubs. Treatment was initiated with subcutaneous vitamin A supplementation and feeding of whole carcasses. Improvement in ataxia was noticed 3 wk later. Follow-up CT and MRI examinations were performed in ML after 3 and 8 mon. The affected bones appeared slightly less thickened and TCR and BBR had decreased to 0.05 after 3 mon. The cerebellum remained mildly herniated, accompanied by amelioration of cervical T2w hyperintensities. After 8 mon, evaluation and diagnostic imaging revealed further improvement regarding the neurologic status and measurements (TCR 0.05, BBR 0.04) despite persistence of a subtle cerebellar herniation. In conclusion, bone remodeling and improvement in clinical signs may be achievable in young lion cubs presented with calvarial hyperostosis and may be attributable to high-dose vitamin A supplementation.

The lack of therapeutics that prevent the development of epilepsy, improve disease prognosis or overcome drug resistance represents an unmet clinical need in veterinary as well as in human medicine. Over the past decade, experimental studies and studies in human epilepsy patients have demonstrated that neuroinflammatory processes are involved in epilepsy development and play a key role in neuronal hyperexcitability that underlies seizure generation. Targeting neuroinflammatory signaling pathways may provide a basis for clinically relevant disease-modification strategies in general, and moreover, could open up new therapeutic avenues for human and veterinary patients with drug-resistant epilepsy. A sound understanding of the neuroinflammatory mechanisms underlying seizure pathogenesis in canine patients is therefore essential for mechanism-based discovery of selective epilepsy therapies that may enable the development of new disease-modifying treatments. In particular, subgroups of canine patients in urgent needs, e.g. dogs with drug-resistant epilepsy, might benefit from more intensive research in this area. Moreover, canine epilepsy shares remarkable similarities in etiology, disease manifestation, and disease progression with human epilepsy. Thus, canine epilepsy is discussed as a translational model for the human disease and epileptic dogs could provide a complementary species for the evaluation of antiepileptic and antiseizure drugs. This review reports key preclinical and clinical findings from experimental research and human medicine supporting the role of neuroinflammation in the pathogenesis of epilepsy. Moreover, the article provides an overview of the current state of knowledge regarding neuroinflammatory processes in canine epilepsy emphasizing the urgent need for further research in this specific field. It also highlights possible functional impact, translational potential and future perspectives of targeting specific inflammatory pathways as disease-modifying and multi-target treatment options for canine epilepsy., Competing Interests: Conflict of interest statement Research on pathophysiological mechanisms of epilepsy and new targeting strategies in Heidrun Potschka’s and Eva-Lotta von Rüden’s group is supported by Deutsche ForschungsgemeinschaftPO 681/12-1. HP received funding for consulting, talks and research collaborations from Eisai, Zogenix, Elanco, Roche, Lario/Exeed Epidarex, Arvelle/Angelini, Jazz Pharmaceuticals, Galapagos, and MSD. AT received funding for a research project from Boehringer-Ingelheim. None of the authors has any other financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Meningoencephalitis of unknown origin (MUO) is an inflammatory disease of the canine central nervous system (CNS) that shares several features with multiple sclerosis (MS) in humans. In approximately 95% of MS patients, ≥ two immunoglobulin G (IgG) oligoclonal bands (OCBs) are detectable exclusively in the cerebrospinal fluid (CSF)., Hypothesis/objectives: To investigate OCBs in CSF and serum in dogs affected by MUO, intervertebral disc disease (IVDD), idiopathic epilepsy (IE), intracranial neoplasia (IN), steroid-responsive meningitis-arteritis (SRMA), and diseases outside the CNS. We hypothesize that the highest prevalence of CSF-specific OCBs (≥ two OCBs uniquely in the CSF) would be found in dogs affected by MUO., Animals: Client-owned dogs (n = 121) presented to the neurology service due to neurological deficits., Methods: Prospective study. Measurement of IgG concentration in CSF and serum via a canine IgG ELISA kit. OCB detection via isoelectric focusing (IEF) and immunoblot., Results: Presence of CSF-specific OCBs was significantly higher in dogs with MUO (57%) compared to 22% in IN, 6% in IE, 15% in SRMA, 13% in IVDD, and 0% in the non-CNS group (p < .001). Dogs with MUO were 9.9 times more likely to show CSF-specific OCBs than all other diseases together (95% confidence interval, 3.7-26.4; p < .001)., Conclusions and Clinical Importance: MUO showed the highest prevalence of CSF-specific OCBs, indicating an inflammatory B cell response. Future studies are needed to evaluate the prevalence in the specific MUO subtypes and a possible similarity with human MS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Prümmer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To investigate emergency clinicians' comfort level in assessing neurological emergencies and to identify opportunities to foster enhanced training of clinical neurology in the emergency room., Design: Internet-based survey., Setting: University teaching hospitals and private referral centers., Subjects: One hundred and ninety-two emergency and critical care specialists and resident trainees (ECC) and 104 neurology specialists and resident trainees (NEUR) in clinical practice., Interventions: An internet-based survey was distributed via veterinary professional organizations' listserves and message boards and responses were collected between March and April 2020. ECC completed a survey evaluating stress levels associated with neurological emergencies, confidence with neurological examinations, and neuroanatomical localization. NEUR completed a similar survey to report their perception of their ECC colleagues' confidence in the assessment of neurological cases. Chi-square and Mann-Whitney U-tests were used to compare categorical responses and confidence scores between groups. P < 0.002 was considered significant., Measurements and Main Results: Fifty-two percent of ECC found neurological emergencies slightly challenging, whereas 85% of NEUR found them moderately to extremely challenging for ECC (P < 0.0001). ECC's median self-reported confidence score in performing a neurologic examination on a scale of 0-100 was 75 (interquartile range [IQR], 27), while NEUR reported a median ECC confidence of 44 (IQR, 25; P < 0.0001). Median self-reported ECC confidence in localizing intracranial, spinal, and neuromuscular disease was 67 (IQR, 40), 88 (IQR, 21), and 60 (IQR, 37), respectively, which was significantly higher than median NEUR-reported ECC confidence of 35 (IQR, 38), 51 (IQR, 31), and 18 (IQR, 20), respectively (all P < 0.0001). Following case transfer, 34% of ECC received NEUR feedback in >75% of cases., Conclusions: Noticeable discrepancies between ECC and NEUR perceptions of ECC clinical confidence were seen, while no firm evidence of neurophobia could be inferred. Improvements in interdepartmental communication and teaching of clinical neurology may be warranted., (© Veterinary Emergency and Critical Care Society 2022.)

Objectives: The aim of this study was to evaluate the association between meningeal enhancement (MgE) and cerebrospinal fluid (CSF) analysis results, their individual association with bacteriology results from affected ear samples and whether these test results influenced clinicians' therapeutic choice in cats with otitis media and interna (OMI)., Methods: This was a multicentre retrospective study carried out over an 8-year period. Cats diagnosed with OMI, with or without a nasopharyngeal polyp, leading to peripheral vestibular signs were included. Only cats for which MRI with postcontrast T1-weighted sequences and CSF analyses available were included. Cats with intra-axial MRI lesions or empyema were excluded., Results: Fifty-eight cats met the inclusion criteria. MgE was reported in 26/58 cases, of which nine had an abnormal CSF result (increased total nucleated cell count [TNCC] or total protein); 32/58 cases had no MgE, of which 10 showed abnormal CSF results. There was no association between bacteriology results (external ear canal or bulla) and MgE or abnormal CSF results. CSF abnormalities were statistically significantly more common in acute cases (n = 16/37) than in chronic cases (n = 3/21; Fischer's test P  = 0.04). Prednisolone was prescribed in 10/16 cases with increased TNCC. Among the 42 cases with normal TNCC, 15 received prednisolone and 13 received non-steroidal anti-inflammatory drugs. Various antimicrobial drugs were prescribed in 53/58 cats. Duration of antimicrobial treatment was similar, regardless of positive bacterial culture (5.58 vs 4.22 weeks), abnormal CSF (5.83 vs 4.76 weeks) or MgE (5.33 vs 4.90 weeks)., Conclusions and Relevance: No association was found between the CSF and MgE results. Furthermore, no association was found between MgE, CSF or bacteriology findings. In addition, abnormal CSF results might lead the clinician to treat with corticosteroids, but they did not have any impact on duration of antimicrobial treatment. CSF abnormalities were seen significantly less frequently in chronic cases. The outcome tended to be poorer when MgE was detected on MRI.

Isoelectric focusing followed by immunoblotting is a method routinely used in human medicine to assess the presence of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) and serum. The detection of OCBs is a valuable diagnostic test, especially important in patients with the suspicion of multiple sclerosis (MS), in which at least two OCBs are found in the CSF not present in paired serum samples in up to 95% of patients. So far, presence of OCBs in CSF and serum of dogs has only been investigated in a small cohort of dogs diagnosed with degenerative myelopathy and healthy dogs. The main objective of the current study was to describe the method used for OCB detection and compare two different canine anti-IgG antibodies: a canine rabbit-anti-IgG antibody (Jackson ImmunoResearch) vs. a canine goat-anti-IgG antibody (Bio-Rad). The method was performed according to the instructions of the commercial kit used. The canine goat-anti-IgG antibody showed a better performance than the canine rabbit-anti-IgG antibody. The availability of the technique of OCB detection in the dog paves the way for further studies, especially in the field of inflammatory diseases of the canine central nervous system, and comparison between specific human and canine diseases., 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 Prümmer, Stein, Marti, Ziegler, Lutterotti, Jelcic, Steffen, Buch and Maiolini.)

Background: Reduced pelvic limb reflexes in dogs with spinal cord injury typically suggests a lesion of the L4-S3 spinal cord segments. However, pelvic limb reflexes might also be reduced in dogs with a T3-L3 myelopathy and concurrent spinal shock., Hypothesis/objectives: We hypothesized that statistical models could be used to identify clinical variables associated with spinal shock in dogs with spinal cord injuries., Animals: Cohort of 59 dogs with T3-L3 myelopathies and spinal shock and 13 dogs with L4-S3 myelopathies., Methods: Data used for this study were prospectively entered by partner institutions into the International Canine Spinal Cord Injury observational registry between October 2016 and July 2019. Univariable logistic regression analyses were performed to assess the association between independent variables and the presence of spinal shock. Independent variables were selected for inclusion in a multivariable logistic regression model if they had a significant effect (P ≤ .1) on the odds of spinal shock in univariable logistic regression., Results: The final multivariable model included the natural log of weight (kg), the natural log of duration of clinical signs (hours), severity (paresis vs paraplegia), and pelvic limb tone (normal vs decreased/absent). The odds of spinal shock decreased with increasing weight (odds ratio [OR] = 0.28, P = .09; confidence interval [CI] 0.07-1.2), increasing duration (OR = 0.44, P = .02; CI 0.21-0.9), decreased pelvic limb tone (OR = 0.04, P = .003; CI 0.01-0.36), and increased in the presence of paraplegia (OR = 7.87, P = .04; CI 1.1-56.62)., Conclusions and Clinical Importance: A formula, as developed by the present study and after external validation, could be useful for assisting clinicians in determining the likelihood of spinal shock in various clinical scenarios and aid in diagnostic planning., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: The diagnosis of idiopathic epilepsy (IE) in dogs is based on exclusion of other potential causes of seizures. Recently, a novel magnetic resonance imaging (MRI) sequence that utilizes a variant of the rotary saturation approach has been suggested to detect weak transient magnetic field oscillations generated by neuronal currents in humans with epilepsy., Hypothesis/objectives: Effects on the magnetic field evoked by intrinsic epileptic activity can be detected by MRI in the canine brain. As proof-of-concept, the novel MRI sequence to detect neuronal currents was applied in dogs., Animals: Twelve dogs with IE and 5 control dogs without a history of epileptic seizures were examined., Methods: Prospective case-control study as proof-of-concept. All dogs underwent a clinical neurological examination, scalp electroencephalography, cerebrospinal fluid analysis, and MRI. The MRI examination included a spin-locking (SL) experiment applying a low-power on-resonance radiofrequency pulse in a predefined frequency domain in the range of oscillations generated by the epileptogenic tissue., Results: In 11 of 12 dogs with IE, rotary saturation effects were detected by the MRI sequence. Four of 5 control dogs did not show rotary saturation effects. One control dog with a diagnosis of neuronal ceroid lipofuscinosis had SL-related effects, but did not have epileptic seizures clinically., Conclusions and Clinical Importance: The proposed MRI method detected neuronal currents in dogs with epileptic seizures and represents a potential new line of research to investigate neuronal currents possibly related to IE in dogs., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective:  The aim of this study was to validate an imaging technique for evaluation of spinal surgery accuracy and to establish accuracy and safety of freehand technique in the thoracolumbar spine of large breed dogs., Study Design:  After thoracolumbar spine computed tomography (CT), 26 drilling corridors were planned then drilled to receive 3.2 mm positive profile pins using a freehand technique. After pin removal, CT was repeated. All entry points, exit points and angles of the preoperative planned trajectories were compared with postoperative ones using an image registration and fusion technique by three observers. Corridor coordinates for entry and exit points were evaluated in three dimensions and angles were measured in one plane. Intraclass correlation coefficient (ICC) was used to establish the imaging technique reliability and descriptive statistics were used to report on the freehand technique accuracy. Safety was evaluated using a vertebral cortical breach grading scheme., Results:  Intraclass correlation coefficient for the entry points, exit points and angle were 0.79, 0.96 and 0.92 respectively. Mean deviations for the entry points, exit points and angle were 3.1 mm, 6.3 mm and 7.6 degrees respectively. Maximum deviations were 6.3 mm, 11.0 mm and 16.4 degrees. Most deviations were lateral and caudal. All corridors were judged as safe., Conclusion:  The imaging technique reliability was good to excellent to study spinal surgery accuracy. Implant deviations should be anticipated when planning stabilization surgery in large breed dogs using the freehand-guided technique., Competing Interests: None declared., (Thieme. All rights reserved.)

Case Summary: A 4-month-old cat was presented with acute paraplegia after the referring veterinarian performed a subcutaneous injection (cefovecin and dexamethasone) in the caudodorsal thoracic area, during which the cat suddenly became uncooperative. A complete neurological examination performed 1 day after the injection revealed paraplegia without deep pain perception and reduced segmental spinal reflexes in the pelvic limbs. Findings were consistent with either an L4-S3 myelopathy or a T3-L3 myelopathy with subsequent spinal shock. MRI showed swelling of the spinal cord from T1 to L1 with heterogeneous T2-weighted intramedullary hyperintensity and no contrast enhancement. A centrally located intraspinal signal void was visible in T2*-weighted images. These changes were compatible with a suspected traumatic intraspinal injection. Despite intensive supportive care over 4 days, neurological status did not improve and the cat was euthanased. Gross pathology findings revealed severe intramedullary haemorrhage and myelomalacia in the T10-L1 spinal cord segments. Histopathology of the spinal cord after haematoxylin and eosin staining revealed a severe intramedullary space-occupying haemorrhage with focal malacia. A trajectory-like, optically empty cavity containing some eosinophilic droplets at the edges was detected. Although no further evidence of trauma was noted in the surrounding structures, the spinal cord changes were compatible with a perforating trauma., Relevance and Novel Information: To our knowledge, this is the first report of thoracic intraspinal injection causing myelomalacia defined by an ante-mortem MRI and confirmed post mortem by histopathology. The traumatic myelopathy appeared to be most compatible with an intraspinal injection causing vascular rupture., Competing Interests: Conflict of interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Epilepsy is a common neurologic disease frequently encountered by small animal practitioners. The disease comprises a multiplicity of clinical presentations and etiologies and often necessitates a comprehensive as well as cost-intensive diagnostic workup. This is mandatory in order to be able to diagnose or exclude a metabolic cause of the seizures and to distinguish between idiopathic and structural epilepsy. The examination by means of magnetic resonance imaging (MRI) represents a central component of the diagnostic workup, which in turn has essential effects on treatment and prognosis. In order to achieve standardized examination and comparable results, it is of utmost importance to use defined MRI protocols. Accordingly, communication and interaction between clinical institutions may be facilitated and as of yet undetected structural changes might be recorded in future MRI techniques. This review article sets particularly emphasis on the definition and classification of epilepsy as well as its diagnostic imaging procedures and refers to statistics and specialists' recommendations for the diagnostic workup in dogs., Competing Interests: Die Autoren erklären, dass sie keine geschützten, finanziellen, beruflichen oder anderen persönlichen Interessen haben, welche die im Manuskript dargestellten Inhalte oder Meinungen beeinflussen könnten., (Thieme. All rights reserved.)

Knowledge of the prognosis of acute spinal cord injury is critical to provide appropriate information for clients and make the best treatment choices. Acute intervertebral disc extrusions (IVDE) are a common cause of pain and paralysis in dogs with several types of IVDE occurring. Important prognostic considerations are recovery of ambulation, return of urinary and fecal continence, resolution of pain and, on the negative side, development of progressive myelomalacia. Initial injury severity affects prognosis as does type of IVDE, particularly when considering recovery of continence. Overall, loss of deep pain perception signals a worse outcome. When considering Hansen type 1 IVDE, the prognosis is altered by the choice of surgical vs. medical therapy. Concentration of structural proteins in the plasma, as well as inflammatory mediators, creatine kinase, and myelin basic protein in the cerebrospinal fluid (CSF) can provide additional prognostic information. Finally, cross-sectional area and length of T2 hyperintensity and loss of HASTE signal on MRI have been associated with outcome. Future developments in plasma and imaging biomarkers will assist in accurate prognostication and optimization of patient management., 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 © 2020 Olby, da Costa, Levine, Stein and the Canine Spinal Cord Injury Consortium (CANSORT SCI).)

Background: Osteomyelitis is relatively frequent in young pigs and a few bacterial species have been postulated to be potential causative agents. Although Actinobacillus (A.) pleuropneumoniae has been sporadically described to cause osteomyelitis, typically, actinobacillosis is characterized by respiratory symptoms. Nevertheless, subclinical infections are a challenging problem in pig herds. To the authors' knowledge, this is the first case description that reports clinical, diagnostic imaging, pathological and histopathological findings of vertebral osteomyelitis in a pig and first describes A. pleuropneumoniae as the causative agent identified by advanced molecular methods., Case Presentation: An eight-week-old female weaner was presented with a non-ambulatory tetraparesis. The neurological signs were consistent with a lesion in the C6-T2 spinal cord segments. Imaging studies revealed a collapse of the seventh cervical vertebral body (C7) with a well demarcated extradural space-occupying mass ventrally within the vertebral canal severely compressing the spinal cord. Post-mortem examination identified an abscess and osteomyelitis of C7 and associated meningitis and neuritis with subsequent pathological fracture of C7 and compression of the spinal cord. In the microbiological analysis, A. pleuropneumoniae was identified using PCR and DNA sequence analysis., Conclusions: A. pleuropneumoniae can be responsible for chronic vertebral abscess formation with subsequent pathological fracture and spinal cord compression in pigs.

Spinal cord injury (SCI) in dogs is commonly attributed to intervertebral disc extrusion (IVDE). Over the last years substantial progress was made in the elucidation of factors contributing to the pathogenesis of this common canine disease. A detailed understanding of the underlying histopathological and molecular alterations in the lesioned spinal cord represents a prerequisite to translate knowledge on the time course of secondary injury processes into the clinical setting. This review summarizes the current state of knowledge of the underlying pathology of canine IVDE-related SCI. Pathological alterations in the spinal cord of dogs affected by IVDE-related SCI include early and persisting axonal damage and glial responses, dominated by phagocytic microglia/macrophages. These processes are paralleled by a pro-inflammatory microenvironment with dysregulation of cytokines and matrix metalloproteinases within the spinal cord. These data mirror findings from a clinical and therapeutic perspective and can be used to identify biomarkers that are able to more precisely predict the clinical outcome. The pathogenesis of progressive myelomalacia, a devastating complication of SCI in dogs, is not understood in detail so far; however, a fulminant and exaggerating secondary injury response with massive reactive oxygen species formation seems to be involved in this unique neuropathological entity. There are substantial gaps in the knowledge of pathological changes in IVDE with respect to more advanced and chronic lesions and the potential involvement of demyelination. Moreover, the role of microglia/macrophage polarization in IVDE-related SCI still remains to be investigated. A close collaboration of clinical neurologists and veterinary pathologists will help to facilitate an integrative approach to a more detailed understanding of the molecular pathogenesis of canine IVDE and thus to identify therapeutic targets., (Copyright © 2020 Spitzbarth, Moore, Stein, Levine, Kühl, Gerhauser, Baumgärtner and the Canine Spinal Cord Injury Consortium (CANSORT-SCI).)

Objectives: To determine whether the neurological examination correctly distinguishes between central and peripheral vestibular lesions in dogs., Materials and Methods: Retrospective study on dogs with vestibular disease presenting to two referral clinics in Germany., Results: Ninety-three dogs were included; neurological examination suggested central vestibular disease in 62 and a peripheral lesion in 31. MRI diagnosis was central vestibular disease in 68 dogs and peripheral in 25. Of the 62 dogs with a lesion localisation diagnosed as central vestibular by neurological exam, 61 were correctly identified (98.4%). Twenty-four of the 31 dogs diagnosed with a peripheral lesion by neurological exam had a consistent lesion on MRI (77.4%)., Clinical Significance: The neurological examination is efficient at identifying lesions in the central vestibular system but less so for peripheral lesions. Therefore it is prudent to recommend imaging in dogs that show signs of peripheral vestibular syndrome but do not rapidly respond to treatment., (© 2020 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

A 1-year-old dwarf rabbit was presented with sub-acute progressive tetraparesis. Radiography, CT and MRI revealed compressive cervical myelopathy secondary to a complex atlanto-axial malformation including partial aplasia of the atlantal dorsal arch, dens malformation, malarticulation and lateral atlanto-occipital displacement. Owners decided against surgical treatment and elected conservative treatment including analgesia with non-steroidal anti-inflammatory drugs, cage rest and physiotherapy. Within 2 months clinical signs deteriorated and the owner elected euthanasia. Subsequent necropsy confirmed imaging findings. Similar cases described in humans and dogs suggest that partial aplasia of the dorsal arch of the atlas might often be an asymptomatic radiologic finding in these species. In contrast, this first description of a similarly affected rabbit demonstrates that complex atlanto-axial malformations can cause severe clinical signs., (© 2018 British Small Animal Veterinary Association.)

Background:  In human medicine, fractures of the second cervical vertebra have been studied elaborately and categorized in detail. This is not the case in veterinary medicine where clinical decisions are often based on old studies focusing on the cervical spine in general., Objectives:  The aim of this study was to describe the clinical features, fracture types, therapeutic options and outcome of dogs and cats with a fractured axis., Study Design:  The present study was a multi-institutional retrospective case series., Results:  Crossbreeds and Labrador Retrievers were the most represented dog breeds. Median age was 2 years. Motor vehicle accident was the most common inciting cause, followed by frontal collision. The most common neurological deficits ranged from cervical pain with or without mild ataxia (22/68) to tetraparesis (28/68) and tetraplegia (11/68). Concerning treatment, 37 of 69 patients underwent surgical fracture stabilization, 27/69 received conservative therapy and 5/69 were immediately euthanatized. Of all treated cases, 52/58 showed ambulatory recovery (23/25 of the conservatively treated and 29/33 of the surgically treated cases), whereby in 40/52 cases full recovery without persisting signs was achieved., Conclusions:  Fractures of the axis commonly occur in young dogs. In many cases, neurological deficits are relatively mild. Generally, animals with a fractured axis have a very good prognosis for functional recovery. The risk of perioperative mortality is considerably lower than previously reported., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders characterized by progressive neurodegeneration and declines in neurological functions. Pathogenic sequence variants in at least 13 genes underlie different forms of NCL, almost all of which are recessively inherited. To date 13 sequence variants in 8 canine orthologs of human NCL genes have been found to occur in 11 dog breeds in which they result in progressive neurological disorders similar to human NCLs. Canine NCLs can serve as models for preclinical evaluation of therapeutic interventions for these disorders. In most NCLs, the onset of neurological signs occurs in childhood, but some forms have adult onsets. Among these is CLN12 disease, also known as Kufor-Rakeb syndrome, PARK9, and spastic paraplegia78. These disorders result from variants in ATP13A2 which encodes a putative transmembrane ion transporter important for lysosomal function. Three Australian Cattle Dogs (a female and two of her offspring) were identified with a progressive neurological disorder with an onset of clinical signs at approximately 6 years of age. The affected dogs exhibited clinical courses and histopathology characteristic of the NCLs. Whole genome sequence analysis of one of these dogs revealed a homozygous c.1118C > T variant in ATP13A2 that predicts a nonconservative p.(Thr373Ile) amino acid substitution. All 3 affected dogs were homozygous for this variant, which was heterozygous in 42 of 394 unaffected Australian Cattle Dogs, the remainder of which were homozygous for the c.1118C allele. The high frequency of the mutant allele in this breed suggests that further screening for this variant should identify additional homozygous dogs and indicates that it would be advisable to perform such screening prior to breeding Australian Cattle Dogs., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

In the current study the hypothesis should be proven that T1 weighted Fast Field Echo (FFE) sequence is a useful method to visualize intervertebral disc degeneration, respectively changes of the expected disc appearance. Medical records of 208 dogs were reviewed and images of 781 intervertebral discs were evaluated by two blinded examiners using a modified Pfirrmann classification system in two MRI sequences: FFE and Turbo-Spin-Echo T2-weighted sequence (T2W). The patients were allocated to three categories based on body conformation: (1) brachycephalic and chondrodystrophic breeds, (2) non-chondrodystrophic and non-brachycephalic breeds with a body weight of < 25 kg, and (3) non-chondrodystrophic and non-brachycephalic breeds with a body weight greater or equal 25 kg. In brachycephalic and chondrodystrophic dogs 340 intervertebral discs were evaluated, the majority of them presented a mild change of the normal disc structure, 53% in the FFE sequence and 41% in T2W images. High discrepancies were observed between mild and moderate degeneration: in the FFE-sequence 15% ( n = 50) of the discs had signs of mild degeneration, whereas in T2W the same discs were graded as moderately degenerated. In non-chondrodystrophic and non-brachycephalic breeds under 25 kg body weight 320 intervertebral discs were assessed. In the FFE-sequence 52% ( n = 166) of the intervertebral discs were judged as having a mild degeneration. In contrast, these same discs were graded as healthy discs (22%), mildly degenerated (33%), moderately degenerated (37%), and severely degenerated (8%) in T2W. In non-chondrodystrophic and non-brachycephalic breeds greater or equal 25 kg 121 intervertebral discs were assessed. The grading was equal in 43%, but differed in one grade (47%) and in two grades (10%) between the two sequences. In both sequences intervertebral disc herniations were equally well-diagnosed. The Kappa coefficient revealed a high discrepancy between the two MRI-sequences. In conclusion, FFE cannot replace the well-established T2W sequence for grading disc degeneration.

Background: Traumatic spinal cord injury (SCI) results in sensory and motor function impairment and may cause a substantial social and economic burden. For the implementation of novel treatment strategies, parallel development of objective tools evaluating spinal cord (SC) integrity during motor function recovery (MFR) is needed. Diffusion tensor imaging (DTI) enables in vivo microstructural assessment of SCI., Methods: In the current study, temporal evolvement of DTI metrics during MFR were examined; therefore, values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in a population of 17 paraplegic dogs with naturally-occurring acute SCI showing MFR within 4 weeks after surgical decompression and compared to 6 control dogs. MRI scans were performed preoperatively and 12 weeks after MFR was observed. DTI metrics were obtained at the lesion epicentre and one SC segment cranially and caudally. Variance analyses were performed to compare values between evaluated localizations in affected dogs and controls and between time points. Correlations between DTI metrics and clinical scores at follow-up examinations were assessed., Results: Before surgery, FA values at epicentres were higher than caudally (p = 0.0014) and control values (p = 0.0097); ADC values were lower in the epicentre compared to control values (p = 0.0035) and perilesional (p = 0.0448 cranially and p = 0.0433 caudally). In follow-up examinations, no significant differences could be found between DTI values from dogs showing MFR and control dogs. Lower ADC values at epicentres correlated with neurological deficits at follow-up examinations (r = - 0.705; p = 0.0023)., Conclusions: Findings suggest that a tendency to the return of DTI values to the physiological situation after surgical decompression accompanies MFR after SCI in paraplegic dogs. DTI may represent a useful and objective clinical tool for follow-up studies examining in vivo SC recovery in treatment studies.

In recent years stem cell therapies have been broadly applied in various disease models specifically immune mediated and degenerative diseases. Whether adipose-derived stem cells might represent a useful therapeutic option in virus-triggered central nervous system diseases has not been investigated so far. Theiler's murine encephalomyelitis (TME) and canine distemper encephalitis are established, virus-mediated animal models sharing many similarities with multiple sclerosis (MS). Canine adipose-derived stem cells (ASC) were selected since dogs might serve as an important translational model for further therapeutic applications. The aim of the present study was to investigate whether canine ASC influence clinical signs, axonal damage, demyelination and inflammation during TME. ASC were transplanted intravenously (iv) or intra-cerebroventricularly (icv) at 7 (early) or 42 (late) days post infection (dpi) in TME virus (TMEV) infected mice. TMEV/ASC iv animals transplanted at 7dpi displayed a transient clinical deterioration in rotarod performance compared to TMEV/control animals. Worsening of clinical signs was associated with significantly increased numbers of microglia/macrophages and demyelination in the spinal cord. In contrast, late transplantation had no influence on clinical findings of TMEV-infected animals. However, late TMEV/ASC iv transplanted animals showed reduced axonal damage compared to TMEV/control animals. Screening of spinal cord and peripheral organs for transplanted ASC revealed no positive cells. Surprisingly, iv transplanted animals showed pulmonary follicular aggregates consisting of T- and B-lymphocytes. Thus, our data suggest that following intravenous application, the lung as priming organ for lymphocytes seems to play a pivotal role in the pathogenesis of TME. Consequences of T-lymphocyte priming in the lung depend on the disease phase and may be responsible for disease modifying effects of ASC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Study Design: Prospective cross-sectional cohort study., Objectives: The canine spontaneous model of spinal cord injury (SCI) is as an important pre-clinical platform as it recapitulates key facets of human injury in a naturally occurring context. The establishment of an observational canine SCI registry constitutes a key step in performing epidemiologic studies and assessing the impact of therapeutic strategies to enhance translational research. Further, accumulating information on dogs with SCI may contribute to current "big data" approaches to enhance understanding of the disease using heterogeneous multi-institutional, multi-species datasets from both pre-clinical and human studies., Setting: Multiple veterinary academic institutions across the United States and Europe., Methods: Common data elements recommended for experimental and human SCI studies were reviewed and adapted for use in a web-based registry, to which all dogs presenting to member veterinary tertiary care facilities were prospectively entered over ~1 year., Results: Analysis of data accumulated during the first year of the registry suggests that 16% of dogs with SCI present with severe, sensorimotor-complete injury and that 15% of cases are seen by a tertiary care facility within 8 h of injury. Similar to the human SCI population, 34% were either overweight or obese., Conclusions: Severity of injury and timing of presentation suggests that neuroprotective studies using the canine clinical model could be conducted efficiently using a multi-institutional approach. Additionally, pet dogs with SCI experience similar comorbidities to people with SCI, in particular obesity, and could serve as an important model to evaluate the effects of this condition.

Background: Transcranial magnetic motor evoked potentials (TMMEP) are associated with severity of clinical signs and magnetic resonance imaging (MRI) findings in dogs with spinal cord disease., Hypothesis: That in initially paraplegic dogs with thoracolumbar intervertebral disc herniation (IVDH), MRI findings before surgery and TMMEPs obtained after decompressive surgery are associated with long-term neurological status and correlate with each other., Animals: Seventeen client-owned paraplegic dogs with acute thoracolumbar IVDH., Methods: Prospective observational study. TMMEPs were obtained from pelvic limbs and MRI (3T) of the spinal cord was performed at initial clinical presentation. Follow-up studies were performed ≤ 2 days after reappearance of motor function and 3 months later. Ratios of compression length, intramedullary hyperintensities' length (T2-weighted hyperintensity length ratio [T2WLR]), and lesion extension (T2-weighted-lesion extension ratio) in relation to the length of the 2nd lumbar vertebral body were calculated., Results: TMMEPs could be elicited in 10/17 (59%) dogs at 1st and in 16/17 (94%) dogs at 2nd follow-up. Comparison of TMMEPs of 1st and 2nd follow-up showed significantly increased amplitudes (median from 0.19 to 0.45 mV) and decreased latencies (from 69.38 to 40.26 ms; P = .01 and .001, respectively). At 2nd follow-up latencies were significantly associated with ambulatory status (P = .024). T2WLR obtained before surgery correlated with latencies at 2nd follow-up (P = .04)., Conclusions: TMMEP reflect motor function recovery after severe spinal cord injury., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Mesenchymal stem cells (MSCs) are regarded as an immune privileged cell type with numerous regeneration-promoting effects. The in vivo behavior of MSC and underlying mechanisms leading to their regenerative effects are largely unknown. The aims of this study were to comparatively investigate the in vivo behavior of canine (cMSC), human (hMSC), and murine MSC (mMSC) following intra-cerebroventricular transplantation. At 7 days post transplantation (dpt), clusters of cMSC, hMSC, and mMSC were detected within the ventricular system. At 49 dpt, cMSC-transplanted mice showed clusters mostly consisting of extracellular matrix lacking transplanted MSC. Similarly, hMSC-transplanted mice lacked MSC clusters at 49 dpt. Xenogeneic MSC transplantation was associated with a local T lymphocyte-dominated immune reaction at both time points. Interestingly, no associated inflammation was observed following syngeneic mMSC transplantation. In conclusion, transplanted MSC formed intraventricular cell clusters and exhibited a short life span in vivo. Xenogeneically in contrast to syngeneically transplanted MSC triggered a T cell-mediated graft rejection indicating that MSCs are not as immune privileged as previously assumed. However, MSC may mediate their effects by a "hit and run" mechanism and future studies will show whether syngeneically or xenogeneically transplanted MSCs exert better therapeutic effects in animals with CNS disease.

Schwann cells are promising candidates for transplantation strategies in the central nervous system by promoting axonal regeneration. The dog represents a translational model for human spinal cord injury (SCI) for studies with new repair strategies after intervertebral disk herniation (IVDH). To overcome the necessity for an additional surgical procedure, for the first time a protocol for the isolation and purification of canine Schwann cells from spinal nerve biopsies during standard hemilaminectomy in IVDH-affected paraplegic dogs for potential transplantation has been developed. Purity was assessed by flow cytometry. The results were compared with biopsies from dogs without SCI. Within 26 ± 4 days, 90.2 ± 8.8% p75 neurotrophin receptor (p75 NTR )-positive cells were achieved in IVDH dogs. The total cell count in acute/subacute and chronic IVDH (acute/subacute: 6.82 ± 6.36 × 10 6 ; chronic: 2.29 ± 2.00 × 10 6 ) differed significantly (p = 0.0120) at the potential time point of transplantation. No differences in culture period and purity were detected between dogs with and without IVDH. Despite the small sample size and the altered environment, the isolation of Schwann cells was successful. Negative influences on isolation and purification due to potential pathological changes at the biopsy site of IVDH-diseased dogs were ruled out by comparison of Schwann cell pellets from diseased and control dogs. Finally, the functionality of Schwann cells from dogs with IVDH was outlined in co-culture experiments with canine dorsal root ganglion neurons. In conclusion, nerve root biopsies provide a sufficient number of highly purified and functional Schwann cells within a useful time period for novel therapeutic strategies in dogs with SCI., (Copyright © 2017 John Wiley & Sons, Ltd.)

In veterinary medicine, patients undergo magnetic resonance imaging (MRI) under general anesthesia to enable acquisition of artifact-free images. The fraction of inspired oxygen (FiO 2 ) ranges between 30 and 95%. In humans, a high FiO 2 is associated with incomplete signal suppression of peripheral cerebrospinal fluid (CSF) spaces on T2-weighted fluid-attenuated inversion recovery (T2w-FLAIR) sequences. The influence of FiO 2 on T2w-FLAIR images remains unreported in small animals. The aim of this prospective study was to investigate whether a high FiO 2 is associated with hyperintensity in peripheral CSF spaces on T2w-FLAIR images in dogs and cats. Client-owned patients undergoing brain MRI were prospectively enrolled. Animals with brain parenchymal abnormalities and/or meningeal contrast enhancement on MRI images and/or abnormal CSF analysis were excluded. Consequently, twelve patients were enrolled. Anesthesia was maintained by isoflurane 0.5-1 minimal alveolar concentration in 30% oxygen. After acquisition of transverse and dorsal T2w-FLAIR images, the FiO 2 was increased to 95%. The T2w-FLAIR sequences were then repeated after 40 min. Arterial blood gas analysis was performed in six patients at the same time as T2w-FLAIR sequence acquisition. Plot profiles of the signal intensity (SI) from CSF spaces of three cerebral sulci and adjacent gray and white matter were generated. SI ratios of CSF space and white matter were compared between the T2w-FLAIR images with 30 and 95% FiO 2 . An observer blinded to the FiO 2 , subjectively evaluated the SI of peripheral CSF spaces on T2w-FLAIR images as high or low. There was significant difference in the partial pressure of oxygen between the two arterial samples ( P  < 0.001). The SI ratios obtained from the T2w-FLAIR images with 95% FiO 2 were significantly higher compared with those obtained from the T2w-FLAIR images with 30% FiO 2 ( P  < 0.05). The peripheral CSF spaces were subjectively considered hyperintense in 11 of 12 cases on T2w-FLAIR images with 95% FiO 2 ( P  < 0.005). A clear difference in SI, dependent on the FiO 2 was seen in the peripheral CSF spaces on T2w-FLAIR images. In conclusion, the influence of FiO 2 must be considered when differentiating pathological and normal CSF spaces on T2w-FLAIR images in dogs and cats.

Study Design: Prospective observational-analytical study., Objectives: Description of diffusion tensor imaging (DTI) metrics obtained from the spinal cord (SC) of dogs with severe acute or chronic spontaneous, non-experimentally induced spinal cord injury (SCI) and correlation of DTI values with lesion extent of SCI measured in T2-weighted (T2W) magnetic resonance imaging sequences., Setting: Hannover, Germany., Methods: Forty-seven paraplegic dogs, 32 with acute and 15 with chronic SCI, and 6 disease controls were included. T2W and DTI sequences of the thoracolumbar spinal cord were performed. Values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were obtained from the epicentre of the lesion and one SC segment cranially and caudally and compared between groups. Pearson's correlation coefficient was calculated between DTI and T2W metrics., Results: During acute SCI, FA values were increased (P=0.0065) and ADC values were decreased (P=0.0099) at epicentres compared to disease controls. FA values obtained from dogs with chronic SCI were lower (P<0.0001 epicentres and caudally; P=0.0002 cranially) and ADC showed no differences compared to disease control values. Dogs with chronic SCI revealed lower FA and higher ADC compared to dogs with acute SCI (P<0.0001 for both values at all localisations). FA values from epicentre and cranially to the lesion during chronic SCI correlated with extent of lesion (r=0.5517; P=0.0052 epicentres and r=0.6810; P=0.0408 cranially)., Conclusion: Using DTI, differences between acute and chronic stages of spontaneous canine SCI were detected and correlations between T2W and DTI sequences were found in chronic SCI, supporting canine SCI as a useful large animal model.

Objectives: Post-traumatic intramedullary myelopathies and cavitations are well described lesions following spinal cord injury (SCI) in humans and have been described in histopathological evaluations in dogs. Human intramedullary myelopathies/cavitations are associated with severe initial SCI and deterioration of clinical signs. Canine intervertebral disc extrusions share similarities with SCI in humans. In this descriptive study, magnetic resonance imaging (MRI) findings in spinal cords of dogs suffering from chronic post-traumatic myelopathies, including cavitations, are elucidated. An additional aim of the study was to compare diagnostic imaging and histopathological findings and identify similarities between human and canine chronic post-traumatic spinal cord lesions., Methods: Thirty-seven dogs with thoracolumbar SCI and one or more 3Tesla MRI investigations more than 3 weeks after SCI were included. Extent of intramedullary lesions and particularly cavitations were evaluated and measured in sagittal and transverse MRI planes. These data were compared with clinical data., Results: A total of 91.9% of study patients developed chronic intramedullary lesions, and 86.5% developed intramedullary cavitations. Paraplegia without deep pain perception at initial examination was significantly associated with longer chronic myelopathies/cavitations (P = 0.002/P = 0.008), and with larger maximal cross-sectional area (mCSA) of the lesions (P = 0.041/0.005). In addition, a non-ambulatory status after decompressive surgery was also associated with the development of longer intramedullary lesions/cavitations (P<0.001) and larger lesion mCSA (P<0.001/P = 0.012). All dogs with negative outcome developed myelopathies/cavitations. In the group of 21 dogs with positive outcome, 3 did not develop any myelopathies, and 5 did not develop cavitations., Conclusions: Development of chronic intramedullary lesions/cavitations are common findings in canine SCI. Extensive chronic intramedullary lesions/cavitations reflect a severe initial SCI and negative clinical outcome. This supports the hypothesis that chronic spinal cord changes following SCI in humans share similarities with canine chronic spinal cord changes after spontaneous intervertebral disc extrusion.

Parasite co-evolution alongside the mammalian immune system gave rise to several modulatory strategies by which they prevent exaggerated pathology and facilitate a longer worm survival. As little is known about the immunoregulatory potential of the zoonotic canine parasites Ancylostoma caninum and Toxocara canis in the natural host, the present study aimed to investigate whether their larval excretory-secretory (ES) products can modulate the canine immune system. We demonstrated TcES to increase the frequency of CD4+ Foxp3 high T cells, while both AcES and TcES were associated with elevated Helios expression in Foxp3 high lymphocytes. ES products were further capable of inducing IL-10 production by lymphocytes, which was mainly attributed to CD8+ T cells. ES treatment of PBMCs prior to mitogen stimulation inhibited polyclonal proliferation of CD4+ and CD8+ T cells. Moreover, monocyte-derived ES-pulsed dendritic cells reduced upregulation of MHC-II and CD80 in response to lipopolysaccharide. The data showed that regulation of the canine immune system by A. caninum and T. canis larvae comprises the modification of antigen-specific and polyclonal T cell responses and dendritic cell maturation.

Macrophages are a heterogeneous cell population playing a pivotal role in tissue homeostasis and inflammation, and their phenotype strongly depends on the micromilieu. Despite its increasing importance as a translational animal model for human diseases, there is a considerable gap of knowledge with respect to macrophage polarization in dogs. The present study comprehensively investigated the morphologic, phenotypic, and transcriptomic characteristics of unstimulated (M0), M1- (GM-CSF, LPS, IFNγ-stimulated) and M2- (M-CSF, IL-4-stimulated)-polarized canine blood-derived macrophages in vitro. Scanning electron microscopy revealed distinct morphologies of polarized macrophages with formation of multinucleated cells in M2-macrophages, while immunofluorescence employing literature-based prototype-antibodies against CD16, CD32, iNOS, MHC class II (M1-markers), CD163, CD206, and arginase-1 (M2-markers) demonstrated that only CD206 was able to discriminate M2-macrophages from both other phenotypes, highlighting this molecule as a promising marker for canine M2-macrophages. Global microarray analysis revealed profound changes in the transcriptome of polarized canine macrophages. Functional analysis pointed out that M1-polarization was associated with biological processes such as "respiratory burst", whereas M2-polarization was associated with processes such as "mitosis". Literature-based marker gene selection revealed only minor overlaps in the gene sets of the dog compared to prototype markers of murine and human macrophages. Biomarker selection using supervised clustering suggested latexin (LXN) and membrane-spanning 4-domains, subfamily A, member 2 (MS4A2) to be the most powerful predicting biomarkers for canine M1- and M2-macrophages, respectively. Immunofluorescence for both markers demonstrated expression of both proteins by macrophages in vitro but failed to reveal differences between canine M1 and M2-macrophages. The present study provides a solid basis for future studies upon the role of macrophage polarization in spontaneous diseases of the dog, a species that has emerging importance for translational research.

Translation of therapeutic interventions for spinal cord injury (SCI) from laboratory to clinic has been historically challenging, highlighting the need for robust models of injury that more closely mirror the human condition. The high prevalence of acute, naturally occurring SCI in pet dogs provides a unique opportunity to evaluate expeditiously promising interventions in a population of animals that receive diagnoses and treatment clinically in a manner similar to persons with SCI, while adhering to National Institutes of Health guidelines for scientific rigor and transparent reporting. In addition, pet dogs with chronic paralysis are often maintained long-term by their owners, offering a similarly unique population for study of chronic SCI. Despite this, only a small number of studies have used the clinical dog model of SCI. The Canine Spinal Cord Injury Consortium (CANSORT-SCI) was recently established by a group of veterinarians and basic science researchers to promote the value of the canine clinical model of SCI. The CANSORT-SCI group held an inaugural meeting November 20 and 21, 2015 to evaluate opportunities and challenges to the use of pet dogs in SCI research. Key challenges identified included lack of familiarity with the model among nonveterinary scientists and questions about how and where in the translational process the canine clinical model would be most valuable. In light of these, we review the natural history, outcome, and available assessment tools associated with canine clinical SCI with emphasis on their relevance to human SCI and the translational process.

Background: Prognostic tools to predict early postoperative motor function recovery (MFR) after thoracolumbar intervertebral disk herniation (IVDH) in paraplegic dogs represent an opportunity to timely implement novel therapies that could shorten recovery times and diminish permanent neurological dysfunctions., Hypothesis: Fractional anisotropy (FA) values obtained using diffusion tensor imaging have a higher prognostic value than a lesion extension ratio in T2-weighted images (T2W-LER) and clinical assessment of deep pain perception (DPP) for MFR., Animals: Thirty-five paraplegic dogs with diagnosis of acute or subacute thoracolumbar IVDH., Methods: Prospective, descriptive observational study. At admission, absence or presence of DPP, T2W-LER, and FA values was evaluated. MFR was assessed within 4 weeks after decompressive surgery. Values of T2W-LER and FA of dogs with and without MFR were compared using t-tests. All 3 methods were evaluated for their sensitivity and specificity as a prognostic factor., Results: No differences were found between groups regarding T2W-LER. FA values differed statistically when measured caudally of lesion epicenter being higher in dogs without MFR compared to dogs with MFR (P = .023). Logistic regression analysis revealed significance in FA values measured caudally of the lesion epicenter (P = .033, area under the curve = 0.72). Using a cutoff value of FA = 0.660, the technique had a sensitivity of 80% and a specificity of 55%. Evaluation of DPP had a sensitivity of 73.3% and specificity of 75% (P = .007)., Conclusions and Clinical Importance: Evaluation of DPP showed a similar sensitivity and a better specificity predicting early MFR than quantitative magnetic resonance imaging., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Transcranial magnetic motor evoked potentials (TMMEPs) can assess the functional integrity of the spinal cord descending motor pathways. In intervertebral disc herniation (IVDH), these pathways are compromised to varying degrees reflected by the severity of neurological deficits. The hypotheses of this study were as follows: (1) TMMEPs differ in dogs with IVDH and healthy control dogs; (2) TMMEPs reflect different severities of neurological signs; and (3) TMMEPs can document functional motor improvement and therefore monitor recovery of function. TMMEPs were recorded in 50 dogs with thoracolumbar IVDH. Clinical signs ranged from spinal hyperesthesia to non-ambulatory paraparesis in 19 dogs and paraplegia with/without deep pain sensation in 31 dogs. In these 31 paraplegic dogs, transcranial magnetic stimulation (TMS) was repeated during follow-up examinations. Ten healthy Beagle dogs served as controls. There was a significant increase in onset latency and decrease in peak-to-peak amplitude in the pelvic limb TMMEPs of dogs with spinal hyperesthesia to severe paraparesis compared to control dogs. Waveforms in dogs with IVDH were predominantly polyphasic in contrast to the biphasic waveforms of the control dogs. TMMEPs could not be generated in the pelvic limbs of paraplegic dogs. However, TMMEPs with markedly increased onset latencies and decreased peak-to-peak amplitudes reappeared in the pelvic limbs of dogs that were paraplegic before surgery and showed functional motor improvement during follow-up. The severity of neurological deficits was reflected by TMMEP findings, which could be used to document functional motor recovery in IVDH. TMS could therefore be used as an ancillary test to monitor response to therapy in dogs during rehabilitation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The aim of this study was to evaluate the influence of two sedation protocols on transcranial magnetic motor evoked potentials (TMMEPs) after transcranial magnetic stimulation in medium sized dogs. Onset latencies and peak-to-peak amplitudes, elicited in the extensor carpi radialis and cranial tibial muscles, were analysed in 10 healthy Beagles that received either acepromazine or dexmedetomidine in combination with levomethadone/fenpipramide, in a crossover design. Similar TMMEP recordings could be made using both sedation protocols at 80-90% stimulation intensity; however, there were significantly shorter onset latencies with the acepromazine-levomethadone/fenpipramide protocol at 100% stimulation intensity. Reference values were established and it was concluded that both drug combinations are feasible for measuring TMMEPs in medium sized dogs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The purpose of this study was to prove the hypothesis that C-reactive protein (CRP) and nerve growth factor (NGF) may be potential biomarkers for lower urinary tract disorders and may be able to distinguish between micturition dysfunctions of different origin in dogs with spinal cord diseases. NGF- and CRP- concentrations were measured in serum and urine samples using specific ELISA-Kits. Results in urine were standardized by urine-creatinine levels., Results: CRP in serum was detectable in 32/76 and in urine samples in 40/76 patients. NGF could be measured in all serum and in 70/76 urine samples. Urinary CRP concentrations were significantly higher in dogs with micturition dysfunction (p = 0.0009) and in dogs with different neurological diseases (p = 0.0020) compared to the control group. However, comparing dogs with spinal cord disorders with and without associated micturition dysfunction no significant difference could be detected for NGF and CRP values in urine or serum samples. Additionally, levels did not decrease significantly, when measured at the time when the dogs regained the ability to urinate properly (urinary NGF p = 0.7962; urinary CRP p = 0.078). Urine samples with bacteria and/or leukocytes had no significant increase in urinary NGF (p = 0.1112) or CRP (p = 0.0534) concentrations, but higher CRP-levels in urine from dogs with cystitis were found compared to dogs without signs of cystitis., Conclusions: From these data we conclude that neither CRP nor NGF in urine or serum can be considered as reliable biomarkers for micturition disorders in dogs with spinal cord disorders in a clinical setting, but their production might be part of the pathogenesis of such disorders. Significantly higher levels of CRP could be found in the urine of dogs with micturition dysfunctions compared to control dogs. This phenomenon could potentially be explained by unspecific extrahepatic CRP production by smooth muscle cells in the dilated bladder.

Motor unit number estimation (MUNE) is an electrophysiological technique to assess the number of motor units innervating a single muscle or muscle group of interest. It may quantify axonal loss in any disease involving injury or degeneration of ventral horn cells or motor axons. Since MUNE has rarely been used in veterinary medicine, our study aimed to evaluate its potential role as an additional diagnostic and prognostic parameter in canine neurology. Therefore, we examined five healthy dogs and seven dogs suffering from diseases that necessitated general anesthesia for further diagnostics and treatment and that were not expected to interfere with the results of electrodiagnostic testing. By using the incremental technique to study MUNE in the cranial tibial muscle, we determined the number of motor units, the size of the compound muscle action potential, and the mean size of individual motor unit potentials of each dog as well as the mean values for each group. Moreover, we studied the correlation between these parameters. Taking the results into consideration, we addressed the difficulties and limitations of this technique. We, furthermore, pointed out possible fields of application for MUNE in canine neurology, and emphasized several aspects that future studies should focus on when applying MUNE to canine patients.

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.

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors' experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible.

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature.There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6-7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed.

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals.The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures.Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements.The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations.

Reactive oxygen species and inflammatory signaling have been identified as pivotal pathophysiological factors contributing to epileptogenesis. Considering the development of combined anti-inflammatory and antioxidant treatment strategies with antiepileptogenic potential, a characterization of the time course of microglial reactive oxygen species generation during epileptogenesis is of major interest. Thus, we isolated microglia cells and analyzed the generation of reactive oxygen species by flow cytometric analysis in an electrical rat post-status epilepticus model. Two days post status epilepticus, a large-sized cell cluster exhibited a pronounced response with excessive production of reactive oxygen species upon stimulation with phorbol-myristate-acetate. Neither in the latency phase nor in the chronic phase with spontaneous seizures a comparable cell population with induction of reactive oxygen species was identified. We were able to demonstrate in the electrical rat post-status-epilepticus model, that microglial ROS generation reaches a peak after the initial insult, is only marginally increased in the latency phase, and returns to control levels during the chronic epileptic phase. The data suggest that a combination of anti-inflammatory and radical scavenging approaches might only be beneficial during a short time window after an epileptogenic brain insult., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)