MFSD2A frameshift variant in Kerry Hill sheep with microcephaly.

Microcephaly is a rare neurodevelopmental disorder characterized by reduced skull circumference and brain volume that occurs sporadically in farm animals. We investigated an early-onset neurodegenerative disorder observed in seven lambs of purebred Kerry Hill sheep. Clinical signs included inability to stand or severe ataxia, convulsions, and early death. Diagnostic imaging and brain necropsy confirmed microcephaly. The pedigree of the lambs suggested monogenic autosomal recessive inheritance. We sequenced the genome of one affected lamb, and comparison with 115 control genomes revealed a single private protein-changing variant. This frameshift variant, MFSD2A: c.285dupA, p.(Asp96fs*9), represents a 1-bp duplication predicted to truncate 80% of the open reading frame. MFSD2A is a transmembrane protein that is essential for maintaining blood-brain barrier homeostasis and plays a key role in regulating brain lipogenesis. Human MFSD2A pathogenic variants are associated with a neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities (NEDMISBA, OMIM 616486). Here we present evidence for the occurrence of a recessively inherited form of microcephaly in sheep due to a loss-of-function variant in MFSD2A (OMIA 002371-9940). To the best of our knowledge, this is the first report of a spontaneous MFSD2A variant in domestic animals.

Case report: A severe case of generalized tetanus in a young cat.

A 10-month-old, 3 kg, female spayed Domestic Shorthair cat was presented with a chronic, infected wound at the level of the proximo-lateral left pelvic limb. General physical examination revealed a weight-bearing lameness of the left pelvic limb, which was moderately and circumferentially swollen and edematous proximal to the tarsal joint. On the lateral aspect of the proximal thigh, there was a chronic wound of 1 cm in diameter and an additional exudative skin lesion was present throughout the whole length of the caudo-lateral thigh. Complete blood count and serum biochemistry profile revealed mild anemia, increased serum amyloid A, hyponatraemia, hypochloraemia, hypocalcaemia, hyperkalaemia, hypermagnesaemia, hyperglycaemia, increased creatine kinase, and increased liver parameters. Surgical exploration of the wound was performed, and necrotizing fasciitis was suspected. The affected limb was amputated and swabs for bacterial culture were taken from both the skin lesions and surgical site before wound closure. One day after surgery, mild muscular contractions on the forehead and an increased muscle tone of the right pelvic limb were evident. One day later, the cat developed a generalized increase in extensor tone, with intermittent opisthotonos, resulting in lateral recumbency. Based on these clinical signs, a diagnosis of generalized tetanus was made and treatment with midazolam, methocarbamol, and metronidazole was started. Despite an improvement of all blood parameters, the cat progressively deteriorated and 4 days after surgery, it developed episodes of tetanic convulsions, associated with hyperthermia and ventricular arrhythmias. Despite intensive care and medical management, the cat died following a cardio-respiratory arrest 3 days later. This case report describes a rare case of severe generalized tetanus in a young cat.

Risk factors, treatment, and outcome in dogs and cats with subdural hematoma and hemispheric collapse after ventriculoperitoneal shunting of congenital internal hydrocephalus.

BACKGROUND: Overshunting and hemispheric collapse are well-known complications after ventriculoperitoneal shunt (VPS) implantation. Risk factors that predispose to overshunting, treatment options, and prognosis after therapeutic intervention have not been described. HYPOTHESIS/OBJECTIVES: To identify preoperative risk factors for overshunting, the effect of surgical decompression, and their outcomes. ANIMALS: Seventy-five dogs and 7 cats. METHODS: Retrospective case cohort study. Age, breed, sex, body weight, number of dilated ventricles, ventricle brain ratio, intraventricular pressure, and implanted pressure valve systems were evaluated as possible risk factors. RESULTS: Overshunting had a prevalence of 18% (Cl 95% 9.9-26.66). An increase of 0.05 in VBR increased the risk of overshunting by OR 2.23 (Cl 95% 1.4-3.5; P = .001). Biventricular hydrocephalus had the highest risk for overshunting compared to a tri- (OR 2.48 with Cl 95% 0.5-11.1) or tetraventricular hydrocephalus (OR 11.6 with Cl 95% 1.7-81.1; P = .05). There was no influence regarding the use of gravitational vs differential pressure valves (P > .78). Overshunting resulted in hemispheric collapse, subdural hemorrhage, and peracute deterioration of neurological status in 15 animals. Subdural hematoma was removed in 8 dogs and 2 cats with prompt postoperative improvement of clinical signs. CONCLUSIONS AND CLINICAL IMPORTANCE: Biventricular hydrocephalus and increased VBR indicate a higher risk for overshunting. The use of differential valves with gravitational units has no influence on occurrence of overshunting related complications and outcomes. Decompressive surgery provides a favorable treatment option for hemispheric collapse and has a good outcome.

Reduced cingulate gyrus volume in Cavalier King Charles Spaniels with syringomyelia and neuropathic pain revealed by voxel-based morphometry: a pilot study.

Objective: Pathomorphological alterations of the central nervous system in dogs, such as syringomyelia and Chiari-like malformation, can cause cranial and cervical hyperesthesia and neuropathic pain. The long-term activity of the pain network can induce functional alteration and eventually even morphological changes in the pain network. This may happen especially in the prefrontal and cingulate cortex, where atrophy of the gray matter (GM) was observed in humans with chronic pain, irrespective of the nature of the pain syndrome. We tested the hypothesis that Cavalier King Charles Spaniels (CKCS) with Chiari-like malformation and associated syringomyelia (SM) and pain show cerebral morphological differences compared to animals without signs of syringomyelia and pain. Methods: Volumetric datasets of 28 different brain structures were analyzed in a retrospective manner, including voxel-based morphometry, using magnetic resonance imaging data obtained from 41 dogs. Results: Volumetric analyses revealed a decrease in GM volumes in the cingulate gyrus (CG) in CKCS with SM and chronic pain when normalized to brain volume. This finding was supported by voxel-based morphometry, which showed a cluster of significance within the CG. Conclusion: GM atrophy in the CG is associated with chronic pain and thus may serve as an objective readout parameter for the diagnosis or treatment of canine pain syndromes.

Temporal lobe epilepsy in cats.

In recent years there has been increased attention to the proposed entity of feline temporal lobe epilepsy (TLE). Epileptic discharges in certain parts of the temporal lobe elicit very similar semiology, which justifies grouping these epilepsies under one name. Furthermore, feline TLE patients tend to have histopathological changes within the temporal lobe, usually in the hippocampus. The initial aetiology is likely to be different but may result in hippocampal necrosis and later hippocampal sclerosis. The aim of this article was not only to summarise the clinical features and the possible aetiology, but also being work to place TLE within the veterinary epilepsy classification. Epilepsies in cats, similar to dogs, are classified based on the aetiology into idiopathic epilepsy, structural epilepsy and unknown cause. TLE seems to be outside of this classification, as it is not an aetiologic category, but a syndrome, associated with a topographic affiliation to a certain anatomical brain structure. Magnetic resonance imaging, histopathologic aspects and current medical therapeutic considerations will be summarised, and emerging surgical options are discussed.

Gabapentinoids Suppress Lipopolysaccharide-Induced Interleukin-6 Production in Primary Cell Cultures of the Rat Spinal Dorsal Horn.

INTRODUCTION: Gabapentin and pregabalin are drugs to treat neuropathic pain. Several studies highlighted effects on presynaptic terminals of nociceptors. Via binding to α2δ subunits of voltage-gated calcium channels, gabapentinoids modulate the synaptic transmission of nociceptive information. However, recent studies revealed further properties of these substances. Treatment with gabapentin or pregabalin in animal models of neuropathic pain resulted not only in reduced symptoms of hyperalgesia but also in an attenuated activation of glial cells and decreased production of pro-inflammatory mediators in the spinal dorsal horn. METHODS: In the present study, we aimed to investigate the impact of gabapentinoids on the inflammatory response of spinal dorsal horn cells, applying the established model of neuro-glial primary cell cultures of the superficial dorsal horn (SDH). We studied effects of gabapentin and pregabalin on lipopolysaccharide (LPS)-induced cytokine release (bioassays), expression of inflammatory marker genes (RT-qPCR), activation of transcription factors (immunocytochemistry), and Ca2+ responses of SDH neurons to stimulation with substance P and glutamate (Ca2+-imaging). RESULTS: We detected an attenuated LPS-induced expression and release of interleukin-6 by SDH cultures in the presence of gabapentinoids. In addition, a significant main effect of drug treatment was observed for mRNA expression of microsomal prostaglandin E synthase 1 and the inhibitor of nuclear factor kappa B. Nuclear translocation of inflammatory transcription factors in glial cells was not significantly affected by gabapentinoid treatment. Moreover, both substances did not modulate neuronal responses upon stimulation with substance P or glutamate. CONCLUSION: Our results provide evidence for anti-inflammatory capacities of gabapentinoids on the acute inflammatory response of SDH primary cultures upon LPS stimulation. Such effects may contribute to the pain-relieving effects of gabapentinoids.

Expression of adipokines and adipocytokines by epidural adipose tissue in cauda equina syndrome in dogs.

BACKGROUND: Compression of epidural adipose tissue (EAT) within the scope of cauda equina syndrome (CES) could lead to an enhanced expression of inflammatory mediators, possibly contributing to pain amplification in dogs. OBJECTIVES: To analyze expression of inflammatory adipo(-cyto)kines within the EAT of dogs with CES. ANIMALS: Client-owned dogs: 15 dogs with CES and 9 dogs euthanized for unrelated medical reasons (controls). METHODS: Prospective, experimental study. Epidural adipose tissue and subcutaneous adipose tissue were collected during dorsal laminectomy and used for real-time quantitative polymerase chain reaction. Tissue explants were cultured for measurements of inflammation-induced release of cytokines. RESULTS: Results show a CES-associated upregulation of the cytokines tumor necrosis factor alpha (TNFα: mean ± SD: 18.88 ± 11.87, 95% CI: 10.90-26.86 vs 9.66 ± 5.22, 95% CI: 5.29-14.02, *: P = .04) and interleukin- (IL-) 10 (20.1 ± 9.15, 95% CI: 14.82-25.39 vs 11.52 ± 6.82, 95% CI: 5.82-17.22, *: P = .03), whereas the expression of the adipokine leptin was attenuated in EAT of dogs with CES (3.07 ± 2.29, 95% CI: 1.80-3.34 vs 9.83 ± 8.42, 95% CI: 3.36-16.30, **: P = .007). Inflammatory stimulation of EAT explant cultures resulted in an enhanced release of IL-6 (LPS: 5491.55 ± 4438, 95% CI: 833.7-10 149; HMGB1: 1001.78 ± 522.2, 95% CI: 518.8-1485; PBS: 310.9 ± 98.57, 95% CI: 228.5-393.3, ***: P < .001). CONCLUSION AND CLINICAL IMPORTANCE: Expression profile of inflammatory adipo(-cyto)kines by EAT is influenced from compressive forces acting in dogs with CES and might contribute to amplification of pain.

Evaluation of Paraspinal Musculature in Small Breed Dogs with and without Atlantoaxial Instability Using Computed Tomography.

OBJECTIVE: The aim of this study was to evaluate differences in paraspinal musculature between dogs with and without atlantoaxial instability (AAI) using computed tomography scans. STUDY DESIGN: Retrospective multicentre study evaluating transverse reconstructed computed tomography scans of 83 small breed dogs (34 with and 49 without AAI) for the cross-sectional paraspinal musculature area at three levels (Occiput/C1, mid-C1, mid-C2). Ratio of moments, dorsal-to-ventral muscle-area ratios (d-v-ratio) and ratios of the dorsal and ventral musculature to C2 height (d-C2-ratio and v-C2-ratio) were evaluated for differences between groups using multivariate analysis of variance (p < 0.05) taking the head-neck position into account. RESULTS: Dogs with AAI showed a significantly lower d-v-ratio at levels 2 and 3, d-C2-ratio at level 2 and ratio of moments at all levels. When head-neck positions were analysed separately, ratio of moments was significantly lower in affected dogs at level 1 and 2. Also lower was d-C2-ratio at level 2, but only in flexed positioning. The head-neck position had a significant influence on ratio of moments and d-v-ratio at all three levels and on d-C2-ratio at level 1. CONCLUSION: Significant changes in muscle area were observed only for the hypaxial muscles at the C1 level, indicating a limited role of muscular adaption in AAI patients. Our results confirm an altered ratio of moments in dogs with AAI. The head-neck position has a significant impact and should be taken into account when evaluating spinal musculature.

Quantitative and qualitative evaluation of the hippocampal cytoarchitecture in adult cats with regard to the pathological diagnosis of hippocampal sclerosis.

Cats are known to be affected by hippocampal sclerosis, potentially causing antiseizure drug(s) resistance. In order to lay the foundation for a standardized, systematic classification and diagnosis of this pathology in cats, this prospective study aimed at evaluating normal reference values of cellular densities and the cytoarchitecture of the feline hippocampus. Three transverse sections (head, body and tail) of each left hippocampus were obtained from 17 non-epileptic cats of different brachycephalic and mesocephalic breeds and age classes (range: 3-17 years). Histological (hematoxylin and eosin, Nissl) and immunohistochemical (NeuN, GFAP) staining was performed to investigate neuron and astroglial cell populations, as well as the layer thickness of the pyramidal cell layer and granule cell layer. Significant differences in neuronal density (in CA2-CA4 and the granule cell layer) and layer thickness (in CA1-CA3 and the granule cell layer) were evidenced throughout the longitudinal hippocampal axis (p<0.05); on the other hand, the astrocyte density did not differ. Moreover, reference ranges were defined for these parameters in the pyramidal cell layer and in the granule cell layer. The findings did not differ according to breed or age. In veterinary medicine these parameters have not been evaluated in cats so far. As surgical treatment may become a therapeutic option for cats with temporal lobe epilepsy, estimating normal values of the hippocampal cytoarchitecture will help in the standardized histopathological examination of resected hippocampal specimens to reach a diagnosis of hippocampal sclerosis.

Determination of cutoff values on computed tomography and magnetic resonance images for the diagnosis of atlantoaxial instability in small-breed dogs.

OBJECTIVE: To determine cutoff values for the diagnosis of atlantoaxial instability (AAI) based on cross-sectional imaging in small-breed dogs. STUDY DESIGN: Retrospective multicenter study. SAMPLE POPULATION: Client-owned dogs (n = 123) and 28 cadavers. METHODS: Dogs were assigned to three groups: a control group, a "potentially unstable" group, and an AAI-affected group, according to imaging findings and clinical signs. The ventral compression index (VCI), cranial translation ratio (CTR), C1-C2 overlap, C1-C2 angle, atlantoaxial distance, basion-dens interval, dens-to-axis length ratio (DALR), power ratio, and clivus canal angles were measured on CT or T2-weighted magnetic resonance (MR) images. Receiver operating characteristic (ROC) analysis was performed to define cutoff values in flexed (≥25°) and extended (<25°) head positions. RESULTS: Cutoff values for the VCI of ≥0.16 in extended and ≥0.2 in flexed head positions were diagnostic for AAI (sensitivity of 100% and 100%, specificity of 94.54% and 96.67%, respectively). Cutoff values for the other measurements were defined with a lower sensitivity (75%-96%) and specificity (70%-97%). A combination of the measurements did not increase the sensitivity and specificity compared with the VCI as single measurement. CONCLUSION: Cutoff values for several imaging measurements were established with good sensitivity and specificity. The VCI, defined as the ratio between the ventral and dorsal atlantodental interval, had the highest sensitivity and specificity in both head positions. CLINICAL SIGNIFICANCE: The use of defined cutoff values allows an objective diagnosis of AAI in small-breed dogs. The decision for surgical intervention, however, should remain based on a combination of clinical and imaging findings.

Closure times of neurocranial sutures and synchondroses in Persian compared to Domestic Shorthair cats.

Human-directed selective breeding has modified the phenotype of the modern Persian cat towards an extreme brachycephalic phenotype ('peke-face' Persian), which originates from a spontaneous mutation that first appeared in the 1950s in traditional Persian types. It was suggested that the peke-face phenotype results from pathologic skull development and might represent a craniosynostosis of the coronal sutures. We followed this hypothesis and investigated the time dependent status of the neurocranial sutures and synchondroses in an ontogenetic series of doll-faced and peke-faced Persian cats compared to Domestic Shorthair cats (DSHs). Cranial suture closure was assessed by examining an ontogenetic series of formalin-fixed head specimens (n = 55) and dry skulls (n = 32) using micro-computed tomography. Sagittal, metopic, coronal and lambdoid sutures as well as intersphenoidal, spheno-occipital and spheno-ethmoid synchondroses were examined. Logistic regression analysis was performed to test the global effect of age on suture closure within a group of peke-face Persians, doll-face Persians and DSHs and the 50% probability of having a closed suture was calculated and compared between groups. Age was a perfect predictor for the condition of the coronal sutures in peke-face Persians. Coronal sutures were found to be closed at 0-0.3 months. In doll-face and DSHs, coronal sutures were open throughout the lifetime with the exception of a few very old cats. Results of this study confirmed a coronal craniosynostosis that likely causes the extreme brachycephalic skull morphology in the peke-face Persian.

Neuroinflammation in Primary Cultures of the Rat Spinal Dorsal Horn Is Attenuated in the Presence of Adipose Tissue-Derived Medicinal Signalling Cells (AdMSCs) in a Co-cultivation Model.

Neuroinflammation within the superficial dorsal horn (SDH) of the spinal cord induces inflammatory pain with symptoms of hyperalgesia and allodynia. Glial activation and production of inflammatory mediators (e.g. cytokines) is associated with modulation of nociceptive signalling. In this context, medicinal signalling cells, e.g. obtained from adipose tissue (AdMSCs), gained attention due to their capacity to modulate the inflammatory response in several diseases, e.g. spinal cord injury. We applied the recently established mixed neuroglial primary cell culture of the rat SDH to investigate effects of AdMSCs on the inflammatory response of SDH cells. Following establishment of a co-cultivation system, we performed specific bioassays for tumour necrosis factor alpha (TNFα) and interleukin (IL)-6, RT-qPCR and immunocytochemistry to detect changes in cytokine production and glial activation upon inflammatory stimulation with lipopolysaccharide (LPS). LPS-induced expression and release of pro-inflammatory cytokines (TNFα, IL-6) by SDH cells was significantly attenuated in the presence of AdMSCs. Further evidence for anti-inflammatory capacities of AdMSCs derived from a blunted LPS-induced TNFα/IL-10 expression ratio and suppressed nuclear translocation of the inflammatory transcription factor nuclear factor kappa B (NFκB) in SDH microglial cells. Expression of IL-10, transforming growth factor beta (TGF-ß) and TNFα-stimulated gene-6 (TSG-6) was detected in AdMSCs, which are putative candidates for anti-inflammatory capacities of these cells. We present a novel co-cultivation system of AdMSCs with neuroglial primary cultures of the SDH to investigate immunomodulatory effects of AdMSCs at a cellular level.

Three-Dimensional Kinematics of the Pelvis and Caudal Lumbar Spine in German Shepherd Dogs.

Lumbosacral vertebral motion is thought to be a factor in the development of degenerative lumbosacral stenosis in German shepherd dogs. So far, few studies exist describing natural canine lumbosacral movement in vivo. Therefore, this investigation aims to achieve a detailed in vivo analysis of bone movement of the lumbosacral region to gain a better understanding of the origin of degenerative lumbosacral stenosis using three-dimensional non-invasive in vivo analysis of canine pelvic and caudal lumbar motion (at L6 and L7). Biplanar cineradiography of the pelvis and caudal lumbar spine of four clinically sound German shepherd dogs at a walk and at a trot on a treadmill was recorded. Pelvic and intervertebral motion was virtually reconstructed and analyzed with scientific rotoscoping. The use of this technique made possible non-invasive measurement of physiological vertebral motion in dogs with high accuracy. Furthermore, the gait patterns of the dogs revealed a wide variation both between individual steps and between dogs. Pelvic motion showed a common basic pattern throughout the stride cycle. Motion at L6 and L7, except for sagittal rotation at a trot, was largely asynchronous with the stride cycle. Intervertebral motion in all dogs was small with approximately 2-3° rotation and translations of approximately 1-2 mm. The predominant motion of the pelvis was axial rotation at a walk, whereas lateral rotation was predominant at a trot. L7 showed a predominance of sagittal rotation (with up to 5.1° at a trot), whereas lateral rotation was the main component of the movement at L6 (about 2.3° in both gaits). During trotting, a coupling of various motions was detected: axial rotation of L7 and the pelvis was inverse and was coupled with craniocaudal translation of L7. In addition, a certain degree of compensation of abnormal pelvic movements during walking and trotting by the caudal lumbar spine was evident.

Three-Dimensional Kinematic Motion of the Craniocervical Junction of Chihuahuas and Labrador Retrievers.

All vertebrate species have a distinct morphology and movement pattern, which reflect the adaption of the animal to its habitat. Yet, our knowledge of motion patterns of the craniocervical junction of dogs is very limited. The aim of this prospective study is to perform a detailed analysis and description of three-dimensional craniocervical motion during locomotion in clinically sound Chihuahuas and Labrador retrievers. This study presents the first in vivo recorded motions of the craniocervical junction of clinically sound Chihuahuas (n = 8) and clinically sound Labrador retrievers (n = 3) using biplanar fluoroscopy. Scientific rotoscoping was used to reconstruct three-dimensional kinematics during locomotion. The same basic motion patterns were found in Chihuahuas and Labrador retrievers during walking. Sagittal, lateral, and axial rotation could be observed in both the atlantoaxial and the atlantooccipital joints during head motion and locomotion. Lateral and axial rotation occurred as a coupled motion pattern. The amplitudes of axial and lateral rotation of the total upper cervical motion and the atlantoaxial joint were higher in Labrador retrievers than in Chihuahuas. The range of motion (ROM) maxima were 20°, 26°, and 24° in the sagittal, lateral, and axial planes, respectively, of the atlantoaxial joint. ROM maxima of 30°, 16°, and 18° in the sagittal, lateral, and axial planes, respectively, were found at the atlantooccipital joint. The average absolute sagittal rotation of the atlas was slightly higher in Chihuahuas (between 9.1 ± 6.8° and 18.7 ± 9.9°) as compared with that of Labrador retrievers (between 5.7 ± 4.6° and 14.5 ± 2.6°), which corresponds to the more acute angle of the atlas in Chihuahuas. Individual differences for example, varying in amplitude or time of occurrence are reported.

Radiographic analysis of the thickness of the cranial bones in captive compared to wild-living cheetahs and in cheetahs with hypovitaminosis A.

Captive cheetahs often demonstrate a high incidence of diseases in which vitamin A imbalances are implicated. These can occur even under controlled and optimised feeding regimens, which is why surveillance of vitamin A status is mandatory in the successful health management of cheetahs. Serum levels of the vitamin do not reflect the true vitamin A status and liver tissue analysis is rather impractical for routine application in large felids. A biomarker for evaluating overt and subclinical vitamin A deficiency in cheetahs is needed. This study evaluates whether increased calvarial bone thickness can be detected on routine skull radiographs of vitamin A deficient cheetahs compared to unaffected animals, and secondly, evaluates whether there is increased bone thickness in clinically sound captive cheetahs in general compared to wild-living controls. Bone thickness in the neuro- and splanchnocranium was measured in 138 skull radiographs. Significant thickening of the parietal bones was found in latero-lateral radiographs of immature cheetahs (< 12 months) with vitamin A deficiency. This finding may allow a presumptive diagnosis of hypovitaminosis A in immature cheetahs. A general difference in skull thickness between free-living and captive cheetahs was not found.

Correlation of brachycephaly grade with level of exophthalmos, reduced airway passages and degree of dental malalignment' in Persian cats.

For many years, there has been a trend to breed cats with an increasing degree of brachycephalic head features, which are known to have a severe impact on the animals' health and welfare. The direct relation between different grades of brachycephaly and their negative implications have not been researched in this species. The aim of this study was therefore to establish correlations between the different grades of brachycephaly and reduced upper respiratory airways, exophthalmos of the eye globes and malalignment of the teeth in Persian cats. Sixty-nine Persian cats of various skull dimensions and ten Domestic shorthair cats were recruited for the study. The cats' skulls were examined using three-dimensional reconstructions created from Computed Tomography datasets. Brachycephaly was graded using established craniometric measurements (facial index, cranial index, skull index, craniofacial angle). The flow area of the nasal passageways at different locations, the amount of the eye globe not supported by the bony orbit and the axial deviation of the teeth were quantified and evaluated for a correlation with the grade of brachycephaly. The results of this study clearly show that increased grades of brachycephaly in Persian cats resulted in larger extra-orbital parts of the ocular bulbs. The brachycephalic skull dimension also resulted in a lower height of the naso-osseal aperture, while other areas of the nasal airways were not correlated with the severity of brachycephaly. Persian cats showed a significantly increased occurrence of premolar tooth displacement in the upper jaw with increasing brachycephaly grades. It was interesting to note that the measured values had a broad range and values of some individual Persian cats showed an overlap with those of Domestic shorthair cats.

Prognostic Biomarkers for Thrombotic Microangiopathy after Acute Graft-versus-Host Disease: A Nested Case-Control Study.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a complication of allogeneic hematopoietic cell transplantation (HCT) that often occurs following the development of acute graft-versus-host disease (aGVHD). In this study, we aimed to identify early TMA biomarkers among patients with aGVHD. We performed a nested-case-control study from a prospective cohort of allogeneic HCT recipients, matching on the timing and severity of antecedent aGVHD. We identified 13 TMA cases and 25 non-TMA controls from 208 patients in the cohort. Using multivariable conditional logistic regression, the odds ratio for TMA compared with non-TMA was 2.65 (95% confidence interval [CI], 1.00 to 7.04) for every 100 ng/mL increase in terminal complement complex sC5b9 and 2.62 (95% CI, 1.56 to 4.38) for every 1000 pg/mL increase in angiopoietin-2 (ANG2) at the onset of aGVHD. ADAMTS13 and von Willebrand factor (VWF) antigens were not appreciably associated with TMA. Using a Cox regression model incorporating sC5b9 >300 ng/mL and ANG2 >3000 pg/mL at the onset of aGVHD, the adjusted hazard ratio for mortality was 5.33 (95% CI, 1.57 to 18.03) for the high-risk group (both elevated) and 4.40 (95% CI, 1.60 to 12.07) for the intermediate-risk group (one elevated) compared with the low-risk group (neither elevated). In conclusion, we found that elevated sC5b9 and ANG2 levels at the onset of aGVHD were associated with the development of TMA and possibly mortality after accounting for the timing and severity of aGVHD. The results suggest important roles of complement activation and endothelial dysfunction in the pathogenesis of TMA. Measurement of these biomarkers at the onset of aGVHD may inform prognostic enrichment for preventive trials and improve clinical care.

Partial cortico-hippocampectomy in cats, as therapy for refractory temporal epilepsy: A descriptive cadaveric study.

Cats, similar to humans, are known to be affected by hippocampal sclerosis (HS), potentially causing antiepileptic drug (AED) resistance. HS can occur as a consequence of chronic seizure activity, trauma, inflammation, or even as a primary disease. In humans, temporal lobe resection is the standardized therapy in patients with refractory temporal lobe epilepsy (TLE). The majority of TLE patients are seizure free after surgery. Therefore, the purpose of this prospective cadaveric study is to establish a surgical technique for hippocampal resection in cats as a treatment for AED resistant seizures. Ten cats of different head morphology were examined. Pre-surgical magnetic resonance imaging (MRI) and computed tomography (CT) studies of the animals' head were carried out to complete 3D reconstruction of the head, brain, and hippocampus. The resected hippocampal specimens and the brains were histologically examined for tissue injury adjacent to the hippocampus. The feasibility of the procedure, as well as the usability of the removed specimen for histopathological examination, was assessed. Moreover, a micro-CT (mCT) examination of the brain of two additional cats was performed in order to assess temporal vasculature as a reason for possible intraoperative complications. In all cats but one, the resection of the temporal cortex and the hippocampus were successful without any evidence of traumatic or vascular lesions in the surrounding neurovascular structures. In one cat, the presence of mechanical damage (a fissure) of the thalamic surface was evident in the histopathologic examination of the brain post-resection. All hippocampal fields and the dentate gyrus were identified in the majority of the cats via histological examination. The study describes a new surgical approach (partial temporal cortico-hippocampectomy) offering a potential treatment for cats with clinical and diagnostic evidence of temporal epilepsy which do not respond adequately to the medical therapy.

Periventricular nodular heterotopia in a Chihuahua.

Periventricular nodular heterotopia is a common neuronal malformation in humans, often leading to epilepsy and other neurologic diseases. A 2-month-old female Chihuahua weighing 750 g was examined because of a history of epileptic seizures and abnormalities in gait and behavior. Results of the clinical examination were consistent with a multifocal neurologic disease with localization in the forebrain and spinovestibular system. The magnetic resonance imaging showed multiple bilateral periventricular nodules isointense to gray matter and ventriculomegaly. Histopathological and immunohistological examination of the brain revealed that periventricular nodules consisted of neurons, fewer astrocytes, and some oligodendroglia consistent with periventricular nodular heterotopias.

Intraoperative measurement of intraventricular pressure in dogs with communicating internal hydrocephalus.

Collapse of the lateral cerebral ventricles after ventriculo-peritoneal drainage is a fatal complication in dogs with internal hydrocephalus. It occurs due to excessive outflow of cerebrospinal fluid into the peritoneal cavity (overshunting). In most shunt systems, one-way valves with different pressure settings regulate flow into the distal catheter to avoid overshunting. The rationale for the choice of an appropriate opening pressure is a setting at the upper limit of normal intracranial pressure in dogs. However, physiological intraventricular pressure in normal dogs vary between 5 and 12 mm Hg. Furthermore, we hypothesise that intraventricular pressure in hydrocephalic dogs might differ from pressure in normal dogs and we also consider that normotensive hydrocephalus exists in dogs, as in humans. In order to evaluate intraventricular pressure in hydrocephalic dogs, twenty-three client owned dogs with newly diagnosed communicating internal hydrocephalus were examined before implantation of a ventriculo-peritoneal shunt using a single use piezo-resistive strain-gauge sensor (MicroSensor ICP probe). Ventricular volume and brain volume were measured before surgery, based on magnetic resonance images. Total ventricular volume was calculated and expressed in relation to the total volume of the brain, including the cerebrum, cerebellum, and brainstem (ventricle-brain index). Multiple logistic regression analysis was performed to assess the influence of the covariates "age", "gender", "duration of clinical signs", "body weight", and "ventricle-brain index" on intraventricular pressure. The mean cerebrospinal fluid pressure in the hydrocephalic dogs was 8.8 mm Hg (standard deviation 4.22), ranging from 3-18 mm Hg. The covariates "age", (P = 0.782), "gender" (P = 0.162), "body weight", (P = 0.065), or ventricle-brain index (P = 0.27)" were not correlated with intraventricular pressure. The duration of clinical signs before surgery, however, was correlated with intraventricular pressure (P< 0.0001). Dogs with internal hydrocephalus do not necessarily have increased intraventricular pressure. Normotensive communicating hydrocephalus exists in dogs.