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In steroid-responsive meningitis-arteritis (SRMA), inflammatory dysregulation is driven by neutrophilic granulocytes resulting in purulent leptomeningitis. Neutrophils can generate neutrophil extracellular traps (NET). Uncontrolled NET-formation or impaired NET-clearance evidently cause tissue and organ damage resulting in immune-mediated diseases. The aim of the study was to verify that NET-formation is detectable in ex vivo samples of acute diseased dogs with SRMA by visualizing and measuring NET-markers in serum and cerebrospinal fluid (CSF) samples. CSF-samples of dogs with acute SRMA (n = 5) and in remission (n = 4) were examined using immunofluorescence (IF)-staining of DNA-histone-1-complexes, myeloperoxidase and citrullinated Histone H3 (H3Cit). Immunogold-labeling of H3Cit and neutrophil elastase followed by transmission electron microscopy (TEM) were used to determine ultrastructural NET-formation in the CSF of one exemplary dog. H3Cit-levels and DNase-activity were measured in CSF and serum samples using an H3Cit-ELISA and a DNase-activity-assay, respectively in patients with the following diseases: acute SRMA (n = 34), SRMA in remission (n = 4), bacterial encephalitis (n = 3), meningioma with neutrophilic inflammation (n = 4), healthy dogs (n = 6). NET-formation was detectable with IF-staining in n = 3/5 CSF samples of dogs with acute SRMA but were not detectable during remission. Vesicular NET-formation was detectable in one exemplary dog using TEM. DNase-activity was significantly reduced in dogs suffering from acute SRMA compared to healthy control group (p < 0.0001). There were no statistical differences of H3Cit levels in CSF or serum samples of acute diseased dogs compared to dogs under treatment, dogs suffering from meningioma or bacterial encephalitis or the healthy control group. Our findings demonstrate that NET-formation and insufficient NET-clearance possibly drive the immunologic dysregulation and complement the pathogenesis of SRMA. The detection of NETs in SRMA offers many possibilities to explore the aetiopathogenetic influence of this defence mechanism of the innate immune system in infectious and non-infectious canine neuropathies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wohlsein 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.)

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.

Idiopathic vestibular syndrome (IVS) is one of the most common neurological disorders in veterinary medicine. However, its diagnosis and treatment varies between publications. The aim of the current study was to gather experts' opinion about IVS definition, diagnosis, and treatment. An online-survey was used to assess neurology specialists' opinion about the definition, diagnosis and treatment of IVS. The study demonstrated that the definition, diagnosis, and treatment of IVS are largely consistent worldwide, with the EU prioritising less frequently advanced imaging and more often otoscopy to rule out other diseases. IVS was defined by most specialists as an acute to peracute, improving, non-painful peripheral vestibular disorder that often affects cats of any age and geriatric dogs. Regarding diagnosis, a detailed neurological examination and comprehensive blood tests, including thyroid values, blood pressure, and otoscopic examination, was seen as crucial. A thorough workup may also involve MRI and CSF analysis to rule out other causes of vestibular dysfunction. Treatment of IVS typically involved intravenous fluid therapy and the use of an antiemetic, with maropitant once daily being the preferred choice among specialists. Antinausea treatment was considered, however, only by a handful specialists. This survey-based study provides valuable insights from neurology experts and highlights areas that require further research to bridge the gap between theory and practice., 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 © 2023 Mertens, Schenk and Volk.)

Epilepsy is a common neurological disorder affecting 0.6-0.75% of dogs in veterinary practice. Treatment is frequently complicated by the occurrence of drug-resistant epilepsy and cluster seizures in dogs with idiopathic epilepsy. Only few studies are available to guide treatment choices beyond licensed veterinary drugs. The aim of the study was to compare antiseizure efficacy and tolerability of two add-on treatment strategies in dogs with drug-resistant idiopathic epilepsy. The study design was a prospective, open-label, non-blinded, comparative treatment trial. Treatment success was defined as a 3-fold extension of the longest baseline interseizure interval and to a minimum of 3 months. To avoid prolonged adherence to a presumably ineffective treatment strategy, dog owners could leave the study after the third day with generalized seizures if the interseizure interval failed to show a relevant increase. Twenty-six dogs (mean age 5.5 years, mean seizure frequency 4/month) with drug-resistant idiopathic epilepsy and a history of cluster seizures were included. Dogs received either add-on treatment with pregabalin (PGB) 4 mg/kg twice daily (14 dogs) or a dose increase in levetiracetam (LEV) add-on treatment (12 dogs). Thirteen dogs in the PGB group had drug levels within the therapeutic range for humans. Two dogs in the PGB group (14.3%; 2/14) and one dog in the LEV group (8.3%; 1/12) achieved treatment success with long seizure-free intervals from 122 to 219 days but then relapsed to their early seizure frequency 10 months after the study inclusion. The overall low success rates with both treatment strategies likely reflect a real-life situation in canine drug-resistant idiopathic epilepsy in everyday veterinary practice. These results delineate the need for research on better pharmacologic and non-pharmacologic treatment strategies in dogs with drug-resistant epilepsy., 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 Kriechbaumer, Jurina, Wielaender, Schenk, Steinberg, Reese, Buhmann, Doerfelt, Potschka and Fischer.)

Objectives: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort., Materials and Methods: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis., Results: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (1.27 to 5.31) and 3.00 (1.22 to 7.89), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (OR 4.56, 1.56 to 14.87)., Clinical Significance: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis., (© 2021 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

A 9-year-old Cairn Terrier was presented for a right thoracic limb lameness of 3-month duration resistant to anti-inflammatory pain treatment. Blood chemistry revealed a highly elevated creatine kinase activity. An orthopedic or vascular etiology of the lameness was excluded by radiographs, computed tomography, and magnetic resonance imaging. Further workup for a neurologic or muscular etiology by electromyography, nerve conduction velocity measurement, and histology of muscle as well as nerve biopsies identified the cause of the lameness. Histology revealed a pyogranulomatous, necrotizing myositis with parasites of the species Trichinella . Furthermore different developmental stages of fungi were detected which were identified as Mucor sp. Treatment with albendazole and itraconazole significantly improved the patient's clinical signs., Competing Interests: Bei keinem der Autoren bestehen direkte finanzielle oder private Interessen oder mittelbare Verbindungen zu Dritten, die die Inhalte dieses Manuskripts beeinflusst haben könnten., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To determine the effects of a minimally invasive transilial vertebral (MTV) blocking procedure on the computed tomographic (CT) appearance of the lumbosacral (L7/S1) junction of dogs with degenerative lumbosacral stenosis (DLSS)., Study Design: Prospective study., Animals: 59 client-owned dogs with DLSS., Methods: Lumbosacral CT images were acquired with hyperextended pelvic limbs before and after MTV in all dogs. Clinical follow-up was obtained after 1 year, including a neurologic status classified in 4 grades, and if possible, CT. Morphometric measurements (Mean ± SEM) including foraminal area, endplate distance at L7/S1 and LS angle were obtained on sets of reformatted parasagittal and sagittal CT images., Results: The mean foraminal area (ForL) increased from 32.5 ± 1.7 mm 2 to 59.7 ± 1.9 mm 2 on the left and from 31.1 ± 1.4 mm 2 to 59.1 ± 2.0 mm 2 on the right (ForR) side after MTV. The mean endplate distance (EDmd) between L7/S1 increased from 3.7 ± 0.1 mm to 6.0 ± 0.1 mm, and mean lumbosacral angle (LSa) from 148.0 ± 1.1° to 170.0 ± 1.1° after MTV. CT measurements were available 1 year postoperatively in 12 cases: ForL: 41.2 ± 3.1 mm 2 ; ForR: 37.9 ± 3.1 mm 2 ; EDmd: 4.3 ± 0.4 mm, and LSa 157.6 ± 2.1° (values are mean and standard error of mean =  SEM). All 39 dogs with long-term follow-up improved by at least 1 neurologic grade, 9/39 improving by 3 grades, 15/39 by 2 grades, and 15/39 by 1 grade., Conclusions: MTV results in clinical improvement and morphometric enlargement of the foraminal area in dogs with variable degrees of foraminal stenosis., Clinical Relevance: MTV may be a valuable minimally invasive option for treatment of dogs with DLSS., (© 2017 The American College of Veterinary Surgeons.)

Background: Peripheral nerve injuries are the most frequent neurologic disorder in cattle. So far, no physiologic values have been established for the motor nerve conduction velocity (mNCV) in this precocial species., Objectives: The electrophysiologic and morphometric reference values of peripheral nerves in calves were determined. It was hypothesized that these parameters would correlate to the high degree of maturity in the first days of life in this species compared to other species., Animals: Twenty-six healthy calves were used in this study., Methods: The mNCV of the radial and the sciatic/common peroneal nerve was measured in all 26 calves. Nerve biopsies from a group of 6 calves were taken to correlate the obtained electrophysiologic data with morphological parameters., Results: The mean mNCV of the radial nerve was 48.3 ± 10.6 m/s, whereas the mean mNCV of the sciatic/peroneal nerve was with 83.8 ± 5.9 m/s significantly faster (P < .0001). The average fiber diameter was 8.40 ± 2.80 μm (range, 1.98-17.90 μm) and the average g-ratio was 0.61 ± 0.04 SD., Conclusion and Clinical Importance: The established reference values for mNCV in calves correlate well with the evaluated morphometric parameters. Attributable to their comparably fast mNCV and high fiber diameters, juvenile calves appear to be much more mature individuals than other mammals. Electrophysiologic characterization of peripheral nerve injury now is feasible in this species., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)

A seven-year old Australian Shepherd, suffering from idiopathic epilepsy under treatment with phenobarbitone and potassium bromide, was presented with generalised lower motor neuron signs. Electrophysiology and muscle-nerve biopsies revealed a neuromyopathy.The serum bromide concentration was increased more than two-fold above the upper reference value.Clinical signs disappeared after applying diuretics and reducing the potassium bromide dose rate. This is the first case report describing electrophysiological and histopathological findings associated with bromide induced lower motor neuron dysfunction in a dog.

Background: The recognition of functional muscular disorders, (e.g. channelopathies like Myotonia) is rising in veterinary neurology. Morphologic (e.g. histology) and even genetic based studies in these diseases are not able to elucidate the functional pathomechanism. As there is a deficit of knowledge and skills considering this special task, the aim of the current pilot study was to develop a canine muscle cell culture system derived from muscle biopsies of healthy client-owned dogs, which allows sampling of the biopsies under working conditions in the daily veterinary practise., Results: Muscular biopsies from 16 dogs of different age and breed were taken during standard surgical procedures and were stored for one to three days at 4°C in a transport medium in order to simulate shipping conditions. Afterwards biopsies were professionally processed, including harvesting of satellite cells, inducing their proliferation, differentiating them into myotubes and recultivating myotubes after long-term storage in liquid nitrogen. Myogenic origin of cultured cells was determined by immunofluorescence, immunohistology and by their typical morphology after inducing differentiation. Subsequent to the differentiation into myotubes feasibility of patch-clamp recordings of voltage gated ion channels was successfully., Conclusion: We have developed a canine muscle cell culture system, which allows sampling of biopsies from young and old dogs of different breeds under practical conditions. Patch clamp measurements can be carried out with the cultured myotubes demonstrating potential of these cells as source for functional research.

The diagnostic value of interictal short time electroencephalographic (EEG) recordings in epileptic dogs under general anaesthesia with propofol and the muscle relaxant rocuronium bromide was investigated. Two activation techniques, namely photic stimulation and hyperventilation, were evaluated for their potential to enhance the diagnostic validity of these recordings. Sixty-one dogs suffering from idiopathic epilepsy and 28 dogs suffering from symptomatic epilepsy were included. Electroencephalograms were recorded using five subdermal EEG electrodes (F3, F4, Cz, O1 and O2). All 89 EEGs were analysed visually and 61 were also evaluated quantitatively with fast Fourier transformation. Interictal paroxysmal epileptiform activity was found in 25% of idiopathic and in 29% of symptomatic epileptic dogs. Quantitative analysis of the EEGs (qEEGs) detected significant differences of frequency analysis in single reading points without any continuous changes of frequency bands. A comparison between healthy and affected brain hemispheres in seven dogs with focal lesions of one hemisphere did not show any significant differences in qEEG analysis. qEEG was not more sensitive than visual evaluation. Despite the use of activation techniques, the results showed that short time EEG recordings in epileptic dogs can detect interictal epileptic activity in less than one third of all seizuring dogs and is not a useful screening method., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: The advantage of minimally invasive electrodiagnostic methods for periodic evaluation of reinnervation at predefined time intervals does not seem to be widely recognized. In this study, using a rat model, we assessed the utility of periodic electrodiagnostic measurements for monitoring ongoing motor recovery after peripheral nerve injuries of differing severity., Methods: In a comparative study, either unilateral sciatic nerve crush injury (n = 10), end-to-end coaptation (n = 5), or 10-mm nerve autotransplantation (n = 10) were performed. During the 6-16-week period thereafter compound muscle action potentials (CMAPs) were recorded percutaneously every week in anesthetized animals. Motor nerve conduction velocity and percentage of axon loss were calculated and compared with footprint analyses (static sciatic index, SSI) and evaluations of sensory recovery., Results: Our results clearly demonstrate that, although SSI measurements reliably demonstrated progress of regeneration after nerve crush injury only, differences in electrodiagnostically determined values precisely remodeled differences in axonal regeneration, which was confirmed by histomorphometric analysis of axonal regeneration., Conclusions: Percutaneous electrodiagnostic measurements enable reliable estimation of axonal regeneration parameters such as myelination and nerve fiber density and display in close proximity the actual status of axonal regeneration., (Copyright © 2011 Wiley Periodicals, Inc.)

Case Description: 12 European shorthair cats (6 males and 6 females; age range, 2 months to 3 years) from 1 household were evaluated for clinical signs of recurrent and progressive muscle spasticity. Genetic relationships among the cats were suspected but were not known., Clinical Findings: Physical examination of all cats revealed a thin to mildly emaciated body condition and signs of suppurative rhinitis. Results of neurologic evaluations revealed no abnormalities in any cats at rest, but exercise- and stress-induced episodes of muscle spasticity were observed. Results of hematologic (7/12 cats) and CSF (4) analysis, diagnostic imaging (including radiography [7] and magnetic resonance imaging [4]), electromyography (4), motor nerve conduction tests (4), screening for metabolic storage diseases (4), provocation tests via exercise in a cold (4°C [39.2°F]) environment (7), and gross pathological and histologic examination (5) revealed no abnormalities that could potentially explain the clinical signs. However, consumption of a potassium-enriched diet resulted in severe aggravation of clinical signs in 7 of 7 cats, leading to a diagnosis of potassium-aggravated muscle stiffness., Treatment and Outcome: 5 cats were euthanized after initial examination because of poor physical condition and severe clinical signs. Spasticity in the 7 remaining cats was improved during a 6-week follow-up period as they reduced their own activity. Further investigation and treatment were declined., Clinical Relevance: Channelopathies are rarely recognized diseases in domestic animals. In addition to conventional diagnostic evaluation methods, provocation tests in a clinical environment can be used in the assessment of channelopathies.

This study was performed to improve a standard anesthetic protocol for electroencephalography (EEG) in dogs and to evaluate the effect of photic stimulation and hyperventilation on the EEG of healthy dogs. Ten clinically and neurologically normal beagle dogs were anesthetized with propofol given intravenously with average doses of 7.5mg/kg for induction and 0.37mg/kg/min constant rate infusion for maintenance. Rocuronium bromide (0.4mg/kg IV) was used as a peripheral muscle relaxant in order to prevent muscle artifacts. EEGs were recorded digitally using five subdermal needle electrodes. Photic stimulation and hyperventilation were performed to evaluate two activation techniques commonly used in human EEG recording methods. Monopolar and bipolar montages were analyzed visually and quantitatively. The use of rocuronium produced muscle artifact-free EEG recordings during the given recording procedure which indicates that rocuronium is a valuable adjunct to anesthesia during EEG recording. Photic stimulation and hyperventilation did not provoke paroxysmal discharges in the EEG of healthy dogs. Analysis of quantitative EEG data showed that background activity did not differ significantly between periods with and without stimulation. This data are important basic values and will further help to compare the effects of photic stimulation and hyperventilation of healthy dogs and those suffering from epilepsy., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep., Methodology/principal Findings: The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6) was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6) staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation., Conclusions/significance: This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery.

Objective: Thiamine deficiency in cats frequently leads to a dysfunction of the central nervous system including vestibular signs with fatal outcome in untreated cases. The aim of the present study was to directly measure thiamine concentrations using high pressure liquid chromatography (HPLC) in feline blood samples and to evaluate values in healthy and diseased cats., Material and Methods: Blood samples (1 ml EDTA-whole blood) from 193 cats were analysed for total thiamine and thiamine diphosphate using HPLC. For the interpretation of the results cats were retrospectively assigned to six groups: A) healthy cats, B) cats with diseases of the gastrointestinal tract, C) cats with different traumas not affecting the gastrointestinal tract, D) cats with inappetence, cats with central vestibular signs and normal (E) or low values of thiamine (F), respectively., Results: In animals of group F no obvious cause for the vestibular signs was found and spontaneous recovery after thiamine application occurred in three cats. Therefore thiamine deficiency was a highly likely clinical diagnosis. Total thiamine concentration (mean 48.2 µg/l, standard deviation ± 22.6) of group F significantly differered from the other groups (group A-D: p<0.01, group E: p<0.001). Comparable results were obtained for thiamine diphosphate. However, low total thiamine values were also found in cats with inappetence without any neurological signs., Conclusion and Clinical Relevance: In the present study a method for direct measurement of thiamine formerly established for ruminants was evaluated for cats. A more accurate and objective clinical diagnosis of thiamine deficiency is feasible in cats with values less than 50 µg/l and typical clinical signs. In animals with values of total thiamine levels between 50-70 µg/l a prophylactic substitution of thiamine can be discussed.

Skeletal muscle cell culture is an important tool to discover the pathogenesis of rare canine neuromuscular diseases. The aim of the current study was to improve an existing clinical protocol to extract and cultivate canine myoblasts by using different enzymes for tissue digestion. The contamination of the mixed culture with fibrocytes should be minimized, a higher number of myoblasts with a shorter lag period should be gained and the influence of transport length on the myoblast numbers should be assessed. Twenty-one muscle biopsies (n = 21) from healthy dogs were taken, mechanically trimmed, enzymatically dissociated with either Protease or Trypsin and cultured under identical conditions for 168 hours. To distinguish and quantify myoblasts and fibrocytes an immunocytochemical staining of the muscle cell specific intermediate filament desmin was performed. To analyse the influence of a transport on the samples eight biopsies were cultured with either Trypsin or Protease at the Using Protease a significant higher production and a morphological better proliferation of myoblasts (P = 0.0102) was achieved. The average percentage of myoblasts was 78.96% using Protease and 54.68% using Trypsin. The duration of the transport (1-3 days) did not result in any significant changes in total myoblast cell counts (P = 0.798). This reveals the possibility to send muscle biopsies from distant clinics to a specialised laboratory. In conclusion, the use of Protease is an improvement for cultivating canine myoblasts and provides better conditions for further investigations elucidating pathogenesis of rare neuromuscular diseases.

A 3-year-old male French bulldog was presented with blindness, staggering and ataxia and was humanely destroyed due to worsening of the neurological signs. At post-mortem examination a non-suppurative leucoencephalitis with extensive malacia within the forebrain was found. In addition, a bilateral necrotizing optic neuritis and focal retinitis was detected. Immunohistochemistry revealed a CD3(+) T-cell dominated inflammatory response with intralesional reactive astrocytes expressing glial fibrillary acidic protein. Astroglia-like cells expressing vimentin, which is characteristic of immature astrocytes, were found within the malacic lesions. The pathological findings are similar to those described in idiopathic necrotizing leucoencephalitis (NLE) of Yorkshire terriers and substantiate the hypothesis that NLE is not a breed-specific disorder that exclusively affects Yorkshire terriers, but also the French bulldog., (Copyright 2009 Elsevier Ltd. All rights reserved.)