COL6A1 related muscular dystrophy in Landseer dogs: A canine model for Ullrich congenital muscular dystrophy.

BACKGROUND: Collagen VI related myopathies are congenital diseases of variable phenotype. The severe phenotype is referred to as Ullrich congenital muscular dystrophy. In this study, we describe analoguos clinical signs and histopathological alterations in Landseer dogs. MATERIALS: We collected clinical data from two affected dogs and investigated the neuromuscular changes in five dogs from two different litters with immunohistochemistry and immunofluorescence. All affected dogs were homozygous for the p.Glu97* nonsense variant in the COL6A1 gene encoding the alpha-1 chain of collagen VI. RESULTS: Muscle biopsies revealed alterations similar to those in human patients with Ullrich congenital muscular dystrophy including the virtual absence of collagen VI in skeletal muscles. CONCLUSIONS: The clinical and pathological characterization of the affected Landseer dogs enhances the value of this animal model for human Ullrich congenital muscular dystrophy.

Influence of a customized three-dimensionally printed drill guide on the accuracy of pedicle screw placement in lumbosacral vertebrae: An ex vivo study.

OBJECTIVE: To compare the accuracy of pedicle screw insertion (PSI) into canine lumbosacral vertebrae with custom-made three-dimensionally (3D)-printed drill guides or freehand insertion. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Nineteen canine lumbosacral specimens. METHODS: Drill guides for PSI were designed on the basis of safe screw insertion trajectories by using preoperative computed tomography (CT) and produced by 3D printing of templates. Right and left sides of the specimens were randomly allocated to two groups; 4-mm pedicle screws were inserted in L5-L6 and L7-S1 spinal segments either freehand (control group) or with custom-made drill guides (guide group). Sixty-six screws were inserted with each method. Insertion angles (α, ß), bone stock, and vertebral canal breach were assessed according to postoperative CT. χ2 Tests were used to compare vertebral canal breach between groups and vertebrae. RESULTS: Breaches in the vertebral canal were less common (P < .001) when screws were placed with a guide in the guide group (9/66, 14%) than without a guide (30/66, 45%). The rate of vertebral canal breach differed at L5 (P = .021) but not at L6 (P = .05), L7 (P = .075) or S1 (P = .658). The angle of insertion (α) did not differ between specimens with and without breaches (guide, P = .068; control, P = .394). CONCLUSION: The use of a customized 3D-printed guide generally improved the accuracy of PSI in canine lumbosacral vertebrae, although statistical significance was reached only at L5. CLINICAL SIGNIFICANCE: The use of customized drill guides may be considered as an alternative to freehand PSI in the lumbosacral area, especially for L5-L6 vertebrae.

Would it be safe to have a dog in the MRI scanner before your own examination? A multicenter study to establish hygiene facts related to dogs and men.

OBJECTIVES: To determine whether it would be hygienic to evaluate dogs and humans in the same MRI scanner. METHODS: We compared the bacterial load in colony-forming units (CFU) of human-pathogenic microorganisms in specimens taken from 18 men and 30 dogs. In addition, we compared the extent of bacterial contamination of an MRI scanner shared by dogs and humans with two other MRI scanners used exclusively by humans. RESULTS: Our study shows a significantly higher bacterial load in specimens taken from men's beards compared with dogs' fur (p = 0.036). All of the men (18/18) showed high microbial counts, whereas only 23/30 dogs had high microbial counts and 7 dogs moderate microbial counts. Furthermore, human-pathogenic microorganisms were more frequently found in human beards (7/18) than in dog fur (4/30), although this difference did not reach statistical significance (p = 0.074). More microbes were found in human oral cavities than in dog oral cavities (p < 0.001). After MRI of dogs, routine scanner disinfection was undertaken and the CFU found in specimens isolated from the MRI scanning table and receiver coils showed significantly lower bacteria count compared with "human" MRI scanners (p < 0.05). CONCLUSION: Our study shows that bearded men harbour significantly higher burden of microbes and more human-pathogenic strains than dogs. As the MRI scanner used for both dogs and humans was routinely cleaned after animal scanning, there was substantially lower bacterial load compared with scanners used exclusively for humans. KEY POINTS: • Bearded men harbour significantly more microbes than dogs. • Dogs are no risk to humans if they use the same MRI. • Deficits in hospital hygiene are a relevant risk for patients.

A missense change in the ATG4D gene links aberrant autophagy to a neurodegenerative vacuolar storage disease.

Inherited neurodegenerative disorders are debilitating diseases that occur across different species. We have performed clinical, pathological and genetic studies to characterize a novel canine neurodegenerative disease present in the Lagotto Romagnolo dog breed. Affected dogs suffer from progressive cerebellar ataxia, sometimes accompanied by episodic nystagmus and behavioral changes. Histological examination revealed unique pathological changes, including profound neuronal cytoplasmic vacuolization in the nervous system, as well as spheroid formation and cytoplasmic aggregation of vacuoles in secretory epithelial tissues and mesenchymal cells. Genetic analyses uncovered a missense change, c.1288G>A; p.A430T, in the autophagy-related ATG4D gene on canine chromosome 20 with a highly significant disease association (p = 3.8 x 10-136) in a cohort of more than 2300 Lagotto Romagnolo dogs. ATG4D encodes a poorly characterized cysteine protease belonging to the macroautophagy pathway. Accordingly, our histological analyses indicated altered autophagic flux in affected tissues. The knockdown of the zebrafish homologue atg4da resulted in a widespread developmental disturbance and neurodegeneration in the central nervous system. Our study describes a previously unknown canine neurological disease with particular pathological features and implicates the ATG4D protein as an important autophagy mediator in neuronal homeostasis. The canine phenotype serves as a model to delineate the disease-causing pathological mechanism(s) and ATG4D function, and can also be used to explore treatment options. Furthermore, our results reveal a novel candidate gene for human neurodegeneration and enable the development of a genetic test for veterinary diagnostic and breeding purposes.

Magnetic resonance imaging features of canine gliomatosis cerebri.

A retrospective, case series study was undertaken to identify magnetic resonance imaging (MRI) characteristics of gliomatosis cerebri in dogs. Fourteen dogs were included by review of histopathological records and contemporaneous MRI. On MRI, all lesions presented as ill-defined, intraaxial lesions within the left and right forebrain hemispheres with involvement of white and gray matter. Lesions presented as hyperintense areas on T2-weighted and FLAIR sequences and as hypointense or isointense areas on T1-weighted images, with mild parenchymal contrast enhancement in three dogs. Signal changes were noted in three to 10 cerebral lobes. Other most commonly affected structures were the thalamus (13), caudate nucleus (13), interthalamic adhesion (11), hypothalamus (11), callosal commissure (10), hippocampus (9), and quadrigeminal plate (8). Abnormalities within the caudal fossa were noted in 10 dogs. Solid tumor portions were identified in five dogs. The histopathological examination demonstrated in all dogs a widespread diffuse infiltration with neoplastic glial cells in white and gray matter with meningeal infiltration. Comparison between MRI and histopathology showed that all areas with signal changes on MRI corresponded to diffuse and dense infiltration with neoplastic cells. The signal intensity on T2-weighted and FLAIR images reflected the density of neoplastic cells. In all dogs, MRI underestimated lesion extent and meningeal infiltration. Involvement of the caudal fossa was not seen on MRI in three dogs. Despite this, MRI allowed identification of lesions extending into at least three cerebral lobes and therefore satisfying the criteria used for diagnosis of diffuse glioma with gliomatosis cerebri growth pattern in humans.

Dielectric Haloscopes: A New Way to Detect Axion Dark Matter.

We propose a new strategy to search for dark matter axions in the mass range of 40-400 µeV by introducing dielectric haloscopes, which consist of dielectric disks placed in a magnetic field. The changing dielectric media cause discontinuities in the axion-induced electric field, leading to the generation of propagating electromagnetic waves to satisfy the continuity requirements at the interfaces. Large-area disks with adjustable distances boost the microwave signal (10-100 GHz) to an observable level and allow one to scan over a broad axion mass range. A sensitivity to QCD axion models is conceivable with 80 disks of 1 m^{2} area contained in a 10 T field.

THREE TESLA MAGNETIC RESONANCE IMAGING FINDINGS IN 12 CASES OF CANINE CENTRAL EUROPEAN TICK-BORNE MENINGOENCEPHALOMYELITIS.

Central European tick-borne encephalomyelitis can be challenging to diagnose in dogs because the virus may not be detected in blood and cerebrospinal fluid (CSF) after the first viremic stage of the disease. The purpose of this retrospective case series study was to describe 3 Tesla magnetic resonance imaging (3T MRI) findings in a sample of dogs with a confirmed diagnosis of tick-borne encephalomyelitis. Dogs were included if they had neurological signs consistent with tick-borne encephalomyelitis, history of a stay in endemic areas for tick-borne encephalomyelitis virus, 3T MRI of the brain and/or spinal cord, cerebrospinal fluid changes compatible with viral infection and positive antibody titers in cerebrospinal fluid or pathologic confirmation of tick-borne encephalomyelitis. Twelve dogs met inclusion criteria. Ten out of 12 patients had 3T MRI lesions at the time of presentation. One patient had persistent lesions in follow-up MRI. The 3T MRI findings included bilateral and symmetrical gray matter distributed lesions involving the thalamus, hippocampus, brain stem, basal nuclei, and ventral horn on the spinal cord. All lesions were hyperintense in T2-weighted sequences compared to white matter, iso- to hypointense in T1-weighted, nonenhancing, and had minimal or no mass effect or perilesional edema. Six patients survived while the remaining six dogs were euthanized. Necropsy revealed neuronophagia and gliosis of the gray matter of the affected regions seen in 3T MRI, in addition to the cerebellum. Findings from the current study indicated that tick-borne encephalomyelitis should be included in the differential diagnosis list for dogs with the above described 3T MRI characteristics.

Neurogenic lower urinary tract dysfunction (NLUTD) in patients with spinal cord injury: long-term urodynamic findings.

OBJECTIVES: To investigate long-term urodynamic findings in patients with spinal cord injury (SCI) with neurogenic lower urinary tract dysfunction (NLUTD). PATIENTS AND METHODS: A consecutive series of 246 patients with SCI (≥5 years since injury) and NLUTD were prospectively evaluated at a single university SCI centre. Data of the latest and earliest available urodynamic investigation were compared. RESULTS: Most of the patients had a thoracic SCI and American Spinal Injury Association (ASIA) impairment scale of A. The mean (sd) duration of SCI to the latest available urodynamic investigation was 17 (10) years and the mean patient age was 51 (14) years. At the earliest and latest available urodynamic investigation, more than half of the patients relied on intermittent self-catheterisation. During the course of disease, there was a relevant increase of patients undergoing onabotulinumtoxinA injections into the detrusor from 12% to 33%. Urodynamic findings at the earliest and latest available urodynamic investigation were within the safe limits and there were significant differences between both groups for maximum cystometric capacity (P < 0.001), compliance (P < 0.001) and maximum detrusor pressure during storage phase (P = 0.008). Vesico-uretero-renal reflux was detected in ≈5% and it was generally low grade. CONCLUSIONS: Most of our regularly followed patients with NLUTD due to SCI for a mean of 17 years had urodynamic findings within the safe limits. Vesico-uretero-renal reflux was quite rare and generally low grade. Thus, regular follow-up with urodynamic investigation allowing for a patient-tailored management seems beneficial warranting randomised controlled longitudinal studies.

LGI2 truncation causes a remitting focal epilepsy in dogs.

One quadrillion synapses are laid in the first two years of postnatal construction of the human brain, which are then pruned until age 10 to 500 trillion synapses composing the final network. Genetic epilepsies are the most common neurological diseases with onset during pruning, affecting 0.5% of 2-10-year-old children, and these epilepsies are often characterized by spontaneous remission. We previously described a remitting epilepsy in the Lagotto romagnolo canine breed. Here, we identify the gene defect and affected neurochemical pathway. We reconstructed a large Lagotto pedigree of around 34 affected animals. Using genome-wide association in 11 discordant sib-pairs from this pedigree, we mapped the disease locus to a 1.7 Mb region of homozygosity in chromosome 3 where we identified a protein-truncating mutation in the Lgi2 gene, a homologue of the human epilepsy gene LGI1. We show that LGI2, like LGI1, is neuronally secreted and acts on metalloproteinase-lacking members of the ADAM family of neuronal receptors, which function in synapse remodeling, and that LGI2 truncation, like LGI1 truncations, prevents secretion and ADAM interaction. The resulting epilepsy onsets at around seven weeks (equivalent to human two years), and remits by four months (human eight years), versus onset after age eight in the majority of human patients with LGI1 mutations. Finally, we show that Lgi2 is expressed highly in the immediate post-natal period until halfway through pruning, unlike Lgi1, which is expressed in the latter part of pruning and beyond. LGI2 acts at least in part through the same ADAM receptors as LGI1, but earlier, ensuring electrical stability (absence of epilepsy) during pruning years, preceding this same function performed by LGI1 in later years. LGI2 should be considered a candidate gene for common remitting childhood epilepsies, and LGI2-to-LGI1 transition for mechanisms of childhood epilepsy remission.

Transarticular fixation with cortical screws combined with dorsal laminectomy and partial discectomy as surgical treatment of degenerative lumbosacral stenosis in 17 dogs: clinical and computed tomography follow-up.

OBJECTIVE: To describe clinical outcome and technical outcome assessed using computed tomography (CT) in dogs with degenerative lumbosacral stenosis (DLSS) treated by dorsal laminectomy, partial discectomy, and transarticular screw fixation. STUDY DESIGN: Retrospective observational case series. ANIMALS: Dogs with DLSS (n = 17). METHODS: Dogs with neurologic and magnetic resonance imaging (MRI) findings compatible with DLSS treated by dorsal laminectomy, partial discectomy and transarticular screw fixation were enrolled. Pre- and postoperative neurologic status was compared. Lumbosacral (LS) angle in extension and misalignment in preoperative MRI were compared with the postoperative CT. Residual mobility of the LS joint after fixation was also evaluated. Status of screws, presence of new bone formation over screw heads/articular facets and presence of adjacent segment disease (ASD) were assessed. RESULTS: Median CT follow-up was 12 months. Clinical improvement was seen in 13 dogs, 2 dogs had intermittent LS pain, and 2 dogs needed revision surgery. In 5 dogs, screws were either pulled out or broken. Reduction of LS angle in extension and misalignment was achieved. Residual mobility of the LS segment was present and ASD was not recognized. CONCLUSIONS: Transarticular screw fixation in dogs with DLSS is associated with a considerable number of technical failures and does not result in rigid stabilization; however, this did not significantly adversely influence clinical outcome.

Peripheral nerve sheath tumor in a subadult golden eagle (Aquila chrysaetos).

A 5-year-old, female golden eagle (Aquila chrysaetos) was admitted with tetraplegia that progressed to a nonambulatory, spastic tetraparesis after a few days of treatment. Clinical and radiologic examinations, including radiography, computed tomography scan, and myelography, were indicative of neoplasia involving a spinal nerve root. Postmortem magnetic resonance imaging and necropsy findings confirmed the diagnosis of a peripheral nerve sheath neoplasia, not, to our knowledge, previously reported in a raptor.

Targeted screening of inflammatory mediators in spontaneous degenerative disc disease in dogs reveals an upregulation of the tumor necrosis superfamily.

Background: The regulation of inflammatory mediators in the degenerating intervertebral disc (IVD) and corresponding ligamentum flavum (LF) is a topic of emerging interest. The study aimed to investigate the expression of a broad array of inflammatory mediators in the degenerated LF and IVD using a dog model of spontaneous degenerative disc disease (DDD) to determine potential treatment targets. Methods: LF and IVD tissues were collected from 22 normal dogs (Pfirrmann grades I and II) and 18 dogs affected by DDD (Pfirrmann grades III and IV). A qPCR gene array was used to investigate the expression of 80 inflammatory genes for LF and IVD tissues, whereafter targets of interest were investigated in additional tissue samples using qPCR, western blot (WB), and immunohistochemistry. Results: Tumor necrosis factor superfamily (TNFSF) signaling was identified as a regulated pathway in DDD, based on the significant regulation (n-fold ± SD) of various TNFSF members in the degenerated IVD, including nerve growth factor (NGF; -8 ± 10), CD40LG (464 ± 442), CD70 (341 ± 336), TNFSF Ligand 10 (9 ± 8), and RANKL/TNFSF Ligand 11 (85 ± 74). In contrast, TNFSF genes were not significantly affected in the degenerated LF compared to the control LF. Protein expression of NGF (WB) was significantly upregulated in both the degenerated LF (4.4 ± 0.5) and IVD (11.3 ± 5.6) compared to the control group. RANKL immunopositivity was significantly upregulated in advanced stages of degeneration (Thompson grades IV and V) in the nucleus pulposus and annulus fibrosus of the IVD, but not in the LF. Conclusions: DDD involves a significant upregulation of various TNFSF members, with tissue-specific expression profiles in LF and IVD tissues. The differential involvement of TNFSF members within multiple spinal tissues from the same individual provides new insights into the inflammatory processes involved in DDD and may provide a basis to formulate hypotheses for the determination of potential treatment targets.

A shortened whole brain radiation therapy protocol for meningoencephalitis of unknown origin in dogs.

Introduction: A variety of treatment options have been described for canine meningoencephalitis of unknown origin (MUO). Few studies focused on radiation therapy as a second line immunomodulating treatment, implicating its effective use. However, a standard radiation therapy protocol is lacking, and further research will help to evaluate the effect of different dose regimens. Methods: Ten dogs diagnosed with MUO based on MRI and CSF findings were prospectively enrolled. The dogs were treated with a shortened whole brain radiation therapy protocol (5 × 4 Gy) in combination with prednisolone. Neurologic changes were quantified using an established scoring scheme. Follow-up MRI and CSF examination was scheduled three months after radiation therapy. Overall survival and time to progression were calculated. Histopathology of the brain was performed in case of death. Results: Seven dogs were diagnosed de novo and three had a history of relapsing MUO. Neurological status improved in all 10 dogs during radiation therapy, with 4/10 returning to normal shortly after radiation therapy. Three dogs died within the first three months after radiation therapy. At follow-up MRI lesions completely resolved in two dogs, partially resolved in five dogs, and progressed in one dog. After follow-up MRI, dogs were further treated with prednisolone monotherapy (two dogs) and additional immunosuppressant drugs (five dogs). Overall, four dogs showed disease progression, with a mean time to progression of 691 days (95%CI: 396-987) and mean overall survival for all dogs was 723 days (95%CI: 436-1011) (both medians not reached). Histopathology confirmed MUO in three dogs but was suggestive for oligodendroglioma in one dog. Radiation induced side effects were not seen. Conclusion: Shortened whole-brain radiation therapy could be an additional treatment option for MUO in conjunction to prednisolone, specifically for cases that require rapid relief of symptoms and with relapsing history.

Manifestations of hypertensive encephalopathy in cats.

OBJECTIVES: Hypertensive encephalopathy in cats is an important entity but is underestimated in clinical practice. This could be explained, in part, by non-specific clinical signs. The objective of this study was to characterise the clinical manifestations of hypertensive encephalopathy in cats. METHODS: Cats with systemic hypertension (SHT) recognised by routine screening, associated with underlying predisposing disease or a clinical presentation suggestive of SHT (neurological or non-neurological), were prospectively enrolled over a 2-year period. Confirmation of SHT was based on at least two sets of measurements of systolic blood pressure >160 mmHg by Doppler sphygmomanometry. RESULTS: Fifty-six hypertensive cats with a median age of 16.5 years were identified; 31 had neurological signs. In 16/31 cats, neurological abnormalities were the primary complaint. The other 15 cats were first presented to the medicine or ophthalmology service, and neurological disease was recognised based on the cat's history. The most common neurological signs were ataxia, various manifestations of seizures and altered behaviour. Individual cats also showed paresis, pleurothotonus, cervical ventroflexion, stupor and facial nerve paralysis. In 28/30 cats, retinal lesions were detected. Of these 28 cats, six presented with a primary complaint of visual deficits, and neurological signs were not the primary complaint; nine presented with non-specific medical issues, without suspicion of SHT-induced organ damage; in 13 cats, neurological issues were the primary complaint and fundic abnormalities were detected subsequently. CONCLUSIONS AND RELEVANCE: SHT is common in older cats and the brain is an important target organ; however, neurological deficits are commonly ignored in cats with SHT. Gait abnormalities, (partial) seizures and even mild behavioural changes should prompt clinicians to consider the presence of SHT. A fundic examination in cats with suspected hypertensive encephalopathy is a sensitive test to support the diagnosis.

Diffusion tensor-based analysis of white matter in dogs with idiopathic epilepsy.

Introduction: The understanding of epileptic seizure pathogenesis has evolved over time, and it is now generally accepted that not only are cortical and subcortical areas involved but also the connection of these regions in the white matter (WM). Recent human neuroimaging studies confirmed the involvement of the WM in several epilepsy syndromes. Neuroimaging studies investigating WM integrity with diffusion tensor imaging (DTI) in canine idiopathic epilepsy are lacking. This study aimed to test the hypothesis that WM diffusion changes can be found in dogs affected by idiopathic epilepsy. Method: Twenty-six dogs with idiopathic epilepsy (15 Border Collies and 11 Greater Swiss Mountain dogs) and 24 healthy controls (11 Beagle dogs, 5 Border Collies, and 8 Greater Swiss Mountain dogs) were prospectively enrolled. Most dogs with idiopathic epilepsy (17/26) were enrolled within 3 months after seizure onset. Diffusion tensor imaging of the brain with 32 diffusion directions (low b value = 0 s/mm2; maximal b value = 800 s/mm2) was performed in a 3 Tesla scanner. Tract-based spatial statistics (TBSS), a voxel-based approach, was used to investigate changes in fractional anisotropy (FA) and mean diffusivity (MD) in the idiopathic epilepsy group compared to the healthy control group. Additionally, FA and MD were investigated in the region of corpus callosum and cingulate white matter in both groups. Results: We observed subtle changes in WM DTI between the idiopathic epilepsy group and the healthy control group limited to cingulate WM, with a significantly lower FA in the idiopathic epilepsy group compared to the healthy control group in the region of interest (ROI) approach (p = 0.027). No significant changes were found between the idiopathic epilepsy group and the healthy control group in the TBSS analysis and in the corpus callosum in the ROI approach. Conclusion: This study supports the cingulate area as a target structure in canine epilepsy. The subtle changes only might be explained by the short duration of epilepsy, small sample sizes, and the higher variability in canine brain anatomy. Furthermore, all included dogs showed generalized tonic-clonic seizures, possibly affected by generalized epilepsy syndrome, which are also associated with less pronounced DTI changes in humans than focal epilepsy syndromes.

Developmental changes in voltage-gated calcium channel α(2)δ-subunit expression in the canine dorsal root ganglion.

The voltage-gated calcium channel subunit α(2)δ plays a fundamental role in propagation of excitatory signals associated with release of glutamate and neuropeptides substance P (SP) and calcitonin gene-related protein (CGRP). It can be selectively inhibited by gabapentinoids. Hence, investigation of the α(2)δ subunit may predict the efficacy of gabapentinoid therapy in neuropathic pain. Since sensory processing underlies significant age-related changes, this study was conducted in order to elucidate the role of the α(2)δ subunit in the sensory transmission during canine development. Dorsal root ganglia (DRG) were harvested from four spinal segments of 16 puppies and 10 adult dogs without a history of neurological signs, pain, spinal disease or orthopedic disorders. α(2)δ-Subunit expression and coexpression with SP and CGRP was evaluated immunohistochemically regarding the number of immunopositive ganglion cells, staining intensity and subcellular distribution. All tested ganglia were immunopositive for α(2)δ. Cell counts and expression levels were significantly lower in pups than in adult dogs (p < 0.05). In the cervical segments of both groups, the number and percentage of immunopositive neurons was significantly higher than in lumbar DRG (p < 0.05). Multilabeling studies in all tested animals confirmed the coexpression of α(2)δ and pain peptides SP and CGRP. This anatomical study for the first time documents the involvement of α(2)δ subunits in sensory signal processing in dogs. The proportion of positive neurons and the intracellular expression levels show a net increase from early postnatal life to adulthood. A significant portion of α(2)δ-positive cells in the dogs exhibited C- and Aδ-phenotypes compatible with nociceptive neurons. The coexpression of α(2)δ, SP and CGRP imply that these neurons are involved with peptidergic nociception. The cervicolumbar gradient of α(2)δ expression in adults reflects functional differences in between forelimbs and hind limbs. These data will facilitate translational studies on neuropathic pain states in this species such as common canine nerve entrapment syndromes.

Intervertebral disc cell- and hydrogel-supported and spontaneous intervertebral disc repair in nucleotomized sheep.

PURPOSE: Regenerative repair is a promising new approach in treating damaged intervertebral discs. An experimental scheme was established for autologous and/or allogenic repair after massive disc injury. METHODS: Disc healing was promoted in 11 animals by injecting in vitro expanded autologous/homologous disc cells 2 weeks after stab injury of lumbar discs L1-2. The following control discs were used in our sheep injury model: L2-3, vehicle only; L3-4, injury only; L4-5, undamaged; and lumbar discs from four non-experimental animals. Disc cells were suspended in a biologically supportive albumin/hyaluronan two-component hydrogel solution that polymerizes when inserted in order to anchor cells at the injection site. The parameters studied were MRI, DNA, glycosaminoglycan, collagen content, histology, immunohistology for collagens type I, II and aggrecan, and mRNA expression of GAPDH, ß-actin, collagen type I, II, X, aggrecan, lubricin, and IL-1ß. RESULTS: All parameters demonstrated almost complete healing of the injured discs after 6 months, when compared with data from both the endogenous non-injured controls as well as from the healthy animals. CONCLUSION: Sheep experience spontaneous recovery from disc injury. The process of endogenous repair can be enhanced by means of hydrogel-supported cells.

Single-Voxel Proton Magnetic Resonance Spectroscopy of the Thalamus in Idiopathic Epileptic Dogs and in Healthy Control Dogs.

The role of magnetic resonance spectroscopy (MRS) in the investigation of brain metabolites in epileptic syndromes in dogs has not been explored systematically to date. The aim of this study was to investigate metabolites in the thalamus in dogs affected by idiopathic epilepsy (IE) with and without antiepileptic drug treatment (AEDT) and to compare them to unaffected controls. Our hypothesis is that similar to humans with generalized epilepsy and loss of consciousness, N-acetyl aspartate (NAA) would be reduced, and glutamate-glutamine (Glx) would be increased in treated and untreated IE in comparison with the control group. In this prospective case-control study, Border Collie (BC) and Greater Swiss Mountain dog (GSMD) were divided into three groups: (1) healthy controls, IE with generalized tonic-clonic seizures with (2) and without (3) AEDT. A total of 41 BC and GSMD were included using 3 Tesla single-voxel proton MRS of the thalamus (PRESS localization, shortest TE, TR = 2000 ms, NSA = 240). After exclusion of 11 dogs, 30 dogs (18 IE and 12 healthy controls) remained available for analysis. Metabolite concentrations were estimated with LCModel using creatine as reference and compared using Kruskal-Wallis and Wilcoxon rank-sum tests. The Kruskal-Wallis test revealed significant differences in the NAA-to-creatine (p = 0.04) and Glx-to-creatine (p = 0.03) ratios between the three groups. The Wilcoxon rank-sum test further showed significant reduction in the NAA/creatine ratio in idiopathic epileptic dogs under AEDT compared to epileptic dogs without AEDT (p = 0.03) and compared to healthy controls (p = 0.03). In opposite to humans, Glx/creatine ratio was significantly reduced in dogs with IE under AEDT compared to epileptic dogs without AEDT (p = 0.03) and controls (p = 0.02). IE without AEDT and healthy controls did not show significant difference, neither in NAA/creatine (p = 0.60), nor in Glx-to-creatine (p = 0.55) ratio. In conclusion, MRS showed changes in dogs with IE and generalized seizures under AEDT, but not in those without AEDT. Based upon these results, MRS can be considered a useful advanced imaging technique for the evaluation of dogs with IE in the clinical and research settings.

Comparison of Two Different Canine Anti-IgG Antibodies for Assessment of Oligoclonal Bands in Cerebrospinal Fluid and Serum of Dogs via Isoelectric Focusing Followed by an Immunoblot.

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.

Concomitant necrotizing encephalitis and granulomatous meningoencephalitis in four toy breed dogs.

The term "meningoencephalitis of unknown origin" (MUO) describes a group of different encephalitides in dogs in which no infectious agent can be identified and a multifactorial etiology is suspected. Among others, genetic factors and unknown triggers seem to be involved. Included are necrotizing leukoencephalitis (NLE), necrotizing meningoencephalitis (NME), and granulomatous meningoencephalitis (GME). In this case series, we describe the histopathological findings of four toy breed dogs with focal or multifocal necrotizing encephalitis and mainly lymphocytic perivascular infiltrates on histopathological examination. At the same time, however, in all dogs, focal or multifocal high-grade angiocentric granulomatous inflammatory lesions were evident with focal histiocytic perivascular infiltrates in the brain. The former changes are typical for NLE and NME. In contrast, the latter changes are indicative of GME. This case series shows that the boundaries between the necrotizing and granulomatous variants of MUO might be smooth and suggests that NLE, NME, and GME are not as distinct as previously described. This finding could be a crucial piece of the puzzle in the study of the pathogenesis of MUO as individual susceptibility and specific triggers could be responsible for the manifestation of the different MUO subtypes.