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.

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.

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.

A stereotaxic breed-averaged, symmetric T2w canine brain atlas including detailed morphological and volumetrical data sets.

Stereotaxic systems and automatic tissue segmentation routines enable neuronavigation as well as reproducible processing of neuroimage datasets. Such systems have been developed for humans, non-human-primates, sheep, and rodents, but not for dogs. Although dogs share important neurofunctional and -anatomical features with humans, and in spite of their importance in translational neuroscience, little is known about the variability of the canine brain morphology and, possibly related, function. Moreover, we lack templates, tissue probability maps (TPM), and stereotaxic brain labels for implementation in standard software utilities such as Statistical Parametric Mapping (SPM). Hence, objective and reproducible, image-based investigations are currently impeded in dogs. We have created a detailed stereotaxic reference frame for dogs including TPM and tissue labels, enabling inter-individual and cross-study neuroimage analysis. T2w datasets were acquired from 16 neurologically inconspicuous dogs of different breeds by 3T MRI. The datasets were averaged after initial preprocessing using linear and nonlinear registration algorithms as implemented in SPM8. TPM for gray (GM) and white matter (WM) as well as cerebrospinal fluid (CSF) were created. Different cortical, subcortical, medullary, and CSF regions were manually labeled to create a spatial binary atlas being aligned with the template. A proof-of-concept for automatic determination of morphological and volumetrical characteristics was performed using additional canine datasets (n = 64) including a subgroup of laboratory beagles (n = 24). Overall, 21 brain regions were labeled using the segmented tissue classes of the brain template. The proof-of-concept trial revealed excellent suitability of the created tools for image processing and subsequent analysis. There was high intra-breed variability in frontal lobe and hippocampus volumes, and noticeable inter-breed corpus callosum volume variation. The T2w brain template provides important, breed-averaged canine brain anatomy features in a spatial standard coordinate system. TPM allows automatic tissue segmentation using SPM and enables unbiased automatic image processing or morphological characterization in different canine breeds. The reported volumetric and morphometric results may serve as a starting point for further research aimed at in vivo analysis of canine brain anatomy and function.

Sensitivity and specificity of magnetic resonance imaging and computed tomography for the determination of the developmental state of cranial sutures and synchondroses in the dog.

BACKGROUND: During skull ontogenesis, growth centers in the skull base and calvarial bones allow gradual expansion of the cranial vault. Premature growth termination of cranial base synchondroses and/or calvarial sutures can result in devastating skull dysmorphologies. There is evidence to believe that a premature closure in one or more cranial growth centers contribute to the brachycephalic skull morphology in dogs. To provide a proof of concept for the non-invasive investigation of ontogenetic changes in cranial sutures and synchondroses in living dogs, we compared magnet resonance imaging (MRI) and computed tomography (CT) with histologic findings. Our aim was to determine the in vitro sensitivity and specificity for conventional clinical imaging methods in the assessment of cranial suture closure and synchondroses ossification in dogs. RESULTS: The evaluation of cranial base synchondroses in MRI had a sensitivity of up to 93.1% and a specificity of 72.7% dependent on the observer. The evaluation of cranial base synchondroses in CT had a sensitivity of 92.2% and a specificity of 86.4%. Suture assessment on MRI suture assessment had a sensitivity of 82.1% dependent on the observer and a specificity of 19.3%. CT suture assessment had a sensitivity of 85.1% and a specificity of 40.4% in dependence of the observer. CONCLUSION: Conventional cross-sectional imaging techniques (MRI and CT) allow reliable assessment of the open or closed state of synchondroses within the cranial base. In contrast CT and MRI are not suitable for a reliable assessment of the cranial sutures in dogs.

Diffusion-weighted imaging of the brains of dogs with idiopathic epilepsy.

BACKGROUND: Idiopathic epilepsy is one of the most common neurological disorders in dogs. Unfortunately, up to 30% of dogs with idiopathic epilepsy show no improvement under antiepileptic drug treatment. Diffusion-weighted imaging is used in human medicine to identify epileptogenic foci in the brain to allow for more invasive treatments such as deep brain stimulation or surgical removal. The aim of this study was to ass the feasibility of interictal diffusion-weighted MRI in dogs and to evaluate the distribution of diffusion in the brains of dogs with idiopathic epilepsy (IE) and to compare these values to previously published values from healthy beagle dogs. Client-owned dogs with the final diagnosis of IE were included in this study. MRI examination was carried out using a 1.0Tesla superconductive magnet. Diffusion-weighted images using a single shot echo planar imaging sequence (SSh-EPI) with a b value of b = 0 s/mm2 and b = 800 s/mm2 were acquired in a dorsal and transverse plane with diffusion gradients in all three planes (x-, y- and z-plane). An ADC (apparent diffusion coefficient) map of the isometric image of each acquired slice was generated. Regions of interest (ROIs) were manually drawn around the caudate nucleus, the thalamus, the piriform lobe including the amygdala, the hippocampus, the semioval center and the temporal cerebral cortex by one of the authors. ROI drawings were repeated 5 times at different time points to assess intra-obersver variability. A multi-way mixed-model analysis of variance (ANOVA) and two-way ANOVA were used during statistical analysis. A p value of p < 0.05 was considered significant. RESULTS: Dogs with IE showed a significantly increased ADC in the amygdala within the piriform lobe and in the semioval center (p < 0.05) compared with the healthy control group. CONCLUSION: Changes in the piriform lobe in cases of epilepsy are reported infrequently in human and veterinary medicine. Similar to our results, ADC changes in the interictal phase usually include an increase in ADC due to cell loss and increased intercellular spaces. Diffusion MRI might be a promising technique for the examination of canine epileptic patients lacking other gross neuromorphological abnormalities.

Magnetic resonance imaging signs of high intraventricular pressure--comparison of findings in dogs with clinically relevant internal hydrocephalus and asymptomatic dogs with ventriculomegaly.

BACKGROUND: Magnetic resonance imaging (MRI) findings of canine brains with enlarged ventricles in asymptomatic dogs were compared to those in dogs with clinically relevant internal hydrocephalus, in order to determine the imaging findings indicative of a relevant increase in intraventricular pressure. Discrimination between clinically relevant hydrocephalus and ventriculomegaly based on MRI findings has not been established yet and is anything but trivial because of the wide variation in ventricular size in different dog breeds and individuals. The MRI scans of the brains of 67 dogs of various breeds, skull conformation and weight were reviewed retrospectively. Based on clinical and imaging findings, the dogs were divided into three groups: a normal group (n = 20), a group with clinically silent ventriculomegaly (n = 25) and a group with severe clinically relevant internal hydrocephalus (n = 22). In addition to the ventricle/brain-index, a number of potential subjective signs of increased intraventricular pressure were recorded and compared between the groups. RESULTS: The ventricle/brain-index was significantly higher in dogs with relevant hydrocephalus (p < 0.001) and a threshold value of 0.6 was specified as a discriminator between internal hydrocephalus and ventriculomegaly. Other MR imaging findings associated with clinically relevant hydrocephalus were an elevation of the corpus callosum (p < 0.01), dorsoventral flattening of the interthalamic adhesion (p < 0.0001), periventricular edema (p < 0.0001), dilation of the olfactory recesses (p < 0.0001), thinning of the cortical sulci (p < 0.0001) and/or the subarachnoid space (p < 0.0027) and disruption of the internal capsule adjacent to the caudate nucleus (p < 0.0001). CONCLUSION: A combination of the abovementioned criteria may support a diagnosis of hydrocephalus that requires treatment.

Focal bacterial meningitis following ascending bite wound infection leading to paraparesis in a captive California sea lion (Zalophus californianus).

Magnetic resonance imaging was performed on a 15-yr-old captive female California sea lion (Zalophus californianus) with a 2-wk history of progressive paraparesis and a 9-mo history of exudative skin lesion on the left thoracic wall. Magnetic resonance images showed a well-defined muscle infiltrating lesion ventrolateral to the seventh cervical to the third thoracic vertebra on the left side, which extended through the left intervertebral foramina C7 to T3 into the vertebral canal, causing spinal cord compression and displacement as well as inflammation of the spinal cord and nerves. This lesion surprisingly caused no forelimb deficits. Differential diagnoses included abscess formation or neoplasia. Pathologic examination revealed chronic focal purulent meningitis associated with widespread paraspinal fistulous inflammation originating from a chronic dermal ulcer. Mainly Escherichia coli var. haemolytica and Clostridium perfringens were identified as the underlying agents.

Vertebral Osteomyelitis and Septic Arthritis Associated With Staphylococcus hyicus in a Juvenile Peregrine Falcon ( Falco peregrinus ).

A 6-week-old, parent-reared peregrine falcon ( Falco peregrinus ) was presented with spastic hypertonus of its hind limbs of unknown origin and duration. Radiologic examination revealed smooth periosteal reactions ventrally at thoracic vertebrae 5 to 7. Contrast-enhanced computed tomography identified the swelling as inflammation; antibiotic, antimycotic, anti-inflammatory, and analgesic treatments were initiated, and vitamins and minerals were supplemented. Because the bird's condition did not improve after 10 days, it was euthanatized and submitted for postmortem examination. On histopathologic examination, chronic, active osteomyelitis was diagnosed in thoracic vertebrae 5 to 7, and chronic, active arthritis was present in both the right shoulder and left elbow joints. Staphylococcus hyicus was isolated from these 3 locations, as well as from lungs and liver, indicating a chronic septic staphylococcosis. Although infections with Staphylococcus species are occasional causes of vertebral osteomyelitis in juvenile poultry with active growth plates, it is only sporadically reported in raptors and companion birds. This case report is the first description of the clinical features and diagnostic and pathologic findings in a juvenile peregrine falcon with hematogenous osteomyelitis and arthritis associated with septicemia caused by S hyicus.

The role of cannabinoid 1 receptor expressing interneurons in behavior.

Schizophrenia is a devastating neurodevelopmental disorder that affects approximately 1% of the population. Reduced expression of the 67-kDa protein isoform of glutamic acid decarboxylase (GAD67) is a hallmark of the disease and is encoded by the GAD1 gene. In schizophrenia, GAD67 downregulation occurs in multiple interneuronal subpopulations, including the cannabinoid receptor type 1 positive (CNR1+) cells, but the functional consequences of these disturbances are not well understood. To investigate the role of the CNR1-positive GABA-ergic interneurons in behavioral and molecular processes, we employed a novel, miRNA-mediated transgenic mouse approach. We silenced the Gad1 transcript using a miRNA engineered to specifically target Gad1 mRNA under the control of Cnr1 bacterial artificial chromosome. Behavioral characterization of our transgenic mice showed elevated and persistent conditioned fear associated with an auditory cue and a significantly altered response to an amphetamine challenge. These deficits could not be attributed to sensory deficits or changes in baseline learning and memory. Furthermore, HPLC analyses revealed that Cnr1/Gad1 mice have enhanced serotonin levels, but not dopamine levels in response to amphetamine. Our findings demonstrate that dysfunction of a small subset of interneurons can have a profound effect on behavior and that the GABA-ergic, monoamine, and cannabinoid systems are functionally interconnected. The results also suggest that understanding the function of various interneuronal subclasses might be essential to develop knowledge-based treatment strategies for various mental disorders including schizophrenia and substance abuse.

Diffusion-weighted magnetic resonance imaging of the normal canine brain.

Diffusion-weighted imaging (DWI) MRI has been primarily reported as a method for diagnosing cerebrovascular disease in veterinary patients. In humans, clinical applications for diffusion-weighted MRI have also included epilepsy, Alzheimer's, and Creutzfeld-Jakob disease. Before these applications can be developed in veterinary patients, more data on brain diffusion characteristics are needed. Therefore, the aim of this study was to evaluate the distribution of diffusion in the normal canine brain. Magnetic resonance imaging of the brain was performed in ten, clinically normal, purpose-bred beagle dogs. On apparent diffusion coefficient maps, regions of interest were drawn around the caudate nucleus, thalamus, piriform lobe, hippocampus, semioval center, and cerebral cortex. Statistically significant differences in mean apparent diffusion coefficient were found for the internal capsule, hippocampus, and thalamus. The highest apparent diffusion coefficient (1044.29 ± 165.21 µm(2)/s (mean ± SD (standard deviation)) was detected in the hippocampus. The lowest apparent diffusion coefficient was measured in the semioval center (721.39 ± 126.28 µm(2)/s (mean ± SD)). Significant differences in mean apparent diffusion coefficients of the caudate nucleus, thalamus, and piriform lobe were found by comparing right and left sides. Differences between brain regions may occur due to differences in myelination, neural density, or fiber orientation. The reason for the differences between right and left sides remains unclear. Data from the current study provide background for further studies of diffusion changes in dogs with brain disease.

Surgical management of primary and idiopathic internal hydrocephalus in dogs and cats.

Ventriculoperitoneal shunt placement is an effective method to treat internal hydrocephalus in dogs and cats. Although it has a long history in veterinary medicine, the technique continues to evolve. Despite continuing attempts to reduce the incidence of associated complications, shunt failure remains a major problem, and often leads to multiple hospital admissions. This review gives an overview about current knowledge of ventriculoperitoneal shunting techniques in animals, applicable shunt hardware as well as shunt-associated complications and their prevention and treatment.

PAX3 haploinsufficiency in Maine Coon cats with dominant blue eyes and hearing loss resembling the human Waardenburg syndrome.

This study investigated the dominant blue eyes (DBE) trait linked to hearing impairment and variable white spotting in Maine Coon cats. Fifty-eight animals descending from two different DBE lineages, the Dutch and the Topaz lines, were sampled. They comprised 48 cats from the Dutch bloodline, including 9 green-eyed and 31 blue-eyed cats, with some individuals exhibiting signs of deafness, and 8 stillborn kittens. Samples from the Topaz lineage included ten blue-eyed animals. A brainstem auditory evoked potential test (BAER) revealed a reduced to absent response to auditory stimuli and absent physiological waveforms in all of the eight examined DBE animals. We sequenced the genome of two affected cats from the Dutch line and searched for variants in 19 candidate genes for the human Waardenburg syndrome and pigmentary disorders. This search yielded nine private protein-changing candidate variants in the genes PAX3, EDN3, KIT, OCA2, SLC24A5, HERC2 and TYRP1. The genotype-phenotype co-segregation was observed for the PAX3 variant within all animals from the Dutch lineage. The mutant allele was absent from 461 control genomes and 241 additionally genotyped green-eyed Maine Coons. We considered the PAX3 variant as the most plausible candidate -a heterozygous nonsense single basepair substitution in exon 6 of PAX3 (NC_051841.1: g.205,787,310G>A, XM_019838731.3:c.937C>T, XP_019694290.1:p.Gln313*), predicted to result in a premature stop codon. PAX3 variants cause auditory-pigmentary syndrome in humans, horses, and mice. Together with the comparative data from other species, our findings strongly suggest PAX3:c.937C>T (OMIA:001688-9685) as the most likely candidate variant for the DBE, deafness and minimal white spotting in the Maine Coon Dutch line. Finally, we propose the designation of DBERE (Rociri Elvis Dominant Blue Eyes) allele in the domestic cat.

Comparison of closure times for cranial base synchondroses in mesaticephalic, brachycephalic, and Cavalier King Charles Spaniel dogs.

Premature closure of cranial base synchondroses has been proposed as the mechanism for brachycephaly in dogs and caudal occipital malformation syndrome (COMS) in Cavalier King Charles Spaniels. The purpose of this retrospective study was to compare times of closure for cranial base synchondroses in mesaticephalic, brachycephalic, and Cavalier King Charles Spaniel dogs. Cranial magnetic resonance imaging studies were retrieved for client-owned dogs less than 18 months of age. Breed, age, skull conformation, and the open or closed state of cranial base synchondroses were independently recorded by two observers. For dogs with a unanimous observer agreement, regression analysis was used to test effects of age and gender on the open or closed status of synchondroses and differences between groups. A total of 174 dogs were included in MRI interpretations and 165 dogs were included in the regression analysis. Statistically significant differences in closure time of the spheno-occipital synchondrosis were identified between brachycephalic and mesaticephalic dogs (P = 0.016), Cavalier King Charles Spaniels and mesaticephalic dogs (P < 0.0001), and Cavalier King Charles Spaniels and brachycephalic dogs (P = 0.014). Findings from the current study supported the theory that morphological changes leading to the skull phenotype of the Cavalier King Charles Spaniels could be due to an earlier closure of the spheno-occipital synchondrosis.

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.

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.

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.

Modeling interneuron dysfunction in schizophrenia.

Schizophrenia is a debilitating neurodevelopmental disorder affecting approximately 1% of the population and imposing a significant burden on society. One of the most replicated and well-established postmortem findings is a deficit in the expression of the gene encoding the 67-kDa isoform of glutamic acid decarboxylase (GAD67), the primary GABA-producing enzyme in the brain. GAD67 is expressed in various classes of interneurons, with vastly different morphological, molecular, and physiological properties. Importantly, GABA system deficits in schizophrenia encompass multiple interneuronal subtypes, raising several important questions. First, do different classes of interneurons regulate different aspects of behavior? Second, can we model cell-type-specific GABAergic deficits in mice, and will the rodent findings translate to human physiology? Finally, will this knowledge open the door to knowledge-based approaches to treat schizophrenia?

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.