Reliability and interobserver variability of a grading system of ventricular distension in dogs.

Introduction: Internal hydrocephalus is the most common malformation of the central nervous system in dogs. Although the grades of ventricular distension have importance for long-term prognosis, there is no standard classification scheme describing the grade of the ventricular distension in dogs. Materials and methods: Magnetic resonance imaging (MRI) scans from 147 dogs of various breed, sex, skull conformation, and weight were reviewed retrospectively and blinded between three observers. Based on objectively assessable morphologic characteristics, the lateral cerebral ventricles were graded as normal, minimally, mildly, moderately, severely enlarged or end stage (grade 0 to grade 5), respectively. Evans' index or the ventricle brain index was also measured in all animals. Interobserver agreement between a very experienced, experienced, and unexperienced person was evaluated by the Spearman coefficient and kappa tests. Additionally, correlation to the ventricle brain index was determined using the Spearman coefficient and F-tests. Results: The Spearman correlation coefficient reached a very strong correlation (r = 0.97) between the experienced and very experienced observer and a strong correlation (r = 0.91) between the very experienced and unexperienced observer. The kappa value revealed excellent interobserver agreement between the very experienced and experienced observers (weighted kappa 0.91) and moderate between the very experienced and unexperienced observers (weighted kappa 0.75). The ventricular-brain index correlated (r = 0.94, Spearman coefficient test) with the grading system, indicating that a more elevated ratio was related to a more advanced degree of ventricular enlargement. The interobserver agreement with regard to the grade between the neurologist in training and a board-certified neurologist was excellent and between the board-certified neurologist and general practitioner achieved lower values. Conclusion: The presented MRI-based grading of ventricular enlargement is a reliable and functional method for an objective grading of the ventricular system in dogs. Some experience in MRI and brain anatomy is needed for interpretation and grading.

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.

Manual therapeutic plasma exchange for treatment of a dog with suspected acute canine polyradiculoneuritis.

BACKGROUND: Acute canine polyradiculoneuritis is one of the most common polyneuropathies occurring in dogs. The disease is very similar to the Guillain-Barré syndrome in humans. In veterinary medicine, there is no established treatment for this disease, while in human medicine, therapeutic plasma exchange and intravenous immunoglobulin administration are two main immunotherapy treatments of this syndrome. CASE PRESENTATION: A 12-year-old male Jack Russel Terrier was presented with a history of acute weakness of the pelvic limbs progressing to flaccid tetraplegia with respiratory compromise. Complete diagnostic workup was performed including blood work, diagnostic imaging (radiographs of the thorax as well as ultrasound of the abdomen) and echocardiography. Based on the clinical course, neurological localisation and the results of electrodiagnostic examination acute canine polyradiculoneuritis was suspected. During the hospitalization, the dog deteriorated and was admitted to the intensive care unit for respiratory support via tracheostomy tube. In addition to symptomatic treatment, immunotherapy via single treatment of manual therapeutic plasma exchange was administered. This procedure was safe, and the dog showed improvement of clinical signs 3 days after therapy was initiated, as well as improvement of neurological signs (from grade 4 tetraplegia to grade 3) within 5 days. However, the dog was euthanized 3 weeks later due to complications related to the tracheostomy. CONCLUSIONS: This is the first case report of a manual therapeutic plasma exchange in a dog with suspected acute canine polyradiculoneuritis suggesting that this method is safe and well tolerated in dogs with this disease. It may be a reasonable adjunctive treatment to supportive therapy in severe cases.

Successful surgical and medical treatment of a severe, acute epidural bleed in a young dog due to steroid responsive meningitis-arteritis.

BACKGROUND: Steroid responsive meningitis-arteritis (SRMA) is an immune-mediated disease of the leptomeninges and its associated blood vessels, typically responsive to corticosteroids. Clinically relevant haemorrhage is a rare finding in such patients and for this reason surgical decompression of the spinal cord is normally not considered. The diagnosis of SRMA is supported by serum C-reactive protein (CRP) increase, cerebrospinal fluid (CSF) examination, including cytology (polymorphonuclear pleocytosis in the acute form), nucleated cell-, red blood cell- and protein count, as well as by evaluating CSF and serum IgA concentrations. D-dimer concentrations in serum and CSF should be elevated as well and therefore can be also evaluated as a further diagnostic tool. CASE PRESENTATION: A 1.5-year-old mixed breed dog was presented with pyrexia, cervical pain and acute tetraparesis. Magnetic resonance imaging revealed an extradural mass lesion at the level of the sixth cervical vertebra, consistent with a subacute epidural haemorrhage, causing severe compression of the spinal cord. Based on the dog's signalment, clinical history and results of the blood and CSF analyses (incl. D-dimer determination), SRMA with secondary epidural haemorrhage was suspected. Decompressive surgery was performed through a right sided partial dorsal laminectomy. Post-surgical immunosuppressive treatment was started with cytarabine and then continued with prednisolone after completion of wound healing. CONCLUSIONS: This is the first report in which medical and surgical treatment were combined in a patient with SRMA and it highlights the possibility of performing a successful surgical intervention despite the need for immunosuppressive therapy. Moreover, while SRMA diagnosis is normally based on CSF analysis and CSF and serum IgA concentrations, D-dimer concentrations in serum and CSF were also useful in this patient.

Interictal Single-Voxel Proton Magnetic Resonance Spectroscopy of the Temporal Lobe in Dogs With Idiopathic Epilepsy.

Proton magnetic resonance spectroscopy (H1-MRS) could provide insight into the metabolic pathophysiology of the temporal lobe of canine brain after seizure. Currently, there is no evidence-based data available on MRS of temporal lobe in dogs with idiopathic epilepsy (IE). The aim of this prospective, cross-sectional study was to evaluate the interictal metabolic activity of the temporal lobe in IE dogs compared to a control group with the use of H1-MRS. Ten healthy dogs and 27 client-owned dogs with IE underwent 1.5-Tesla magnetic resonance imaging (MRI) and single-voxel H1-MRS. The MRS studies were acquired as spin echoes with a repetition time (TR) of 2,000 ms and an echo time (TE) of 144 ms. A cubic voxel (10 ×10 ×10 mm) was positioned bilaterally into the region of the left and right temporal lobe, including a middle part of the hippocampus and the amygdala. The N-acetylaspartate (NAA)-to-creatine (NAA/Cr), NAA-to-choline (NAA/Cho), choline-to-creatine (Cho/Cr), and choline-to-NAA (Cho/NAA) ratios were determined in both hemispheres and compared to controls. No significant differences in all metabolite ratios between epileptic dogs and the control group could be found. A time-dependent decrease in the NAA/Cho ratio as well as an increase in the Cho/NAA ratio was found with proximity in time to the last seizure. We found no correlation between metabolite ratios and age or sex in this animal group. Time span from the last seizure to the acquisition of MRS significantly correlated with NAA/Cho and Cho/NAA ratio. We conclude that without a time relation, metabolite ratios in dogs with IE do not differ from those of the control group.

Spontaneous hemispheric ventricular collapse and subarachnoid haemorrhages in a dog with congenital hydrocephalus internus.

BACKGROUND: Overdrainage and collapse of the hemispheres is a potential severe complication after surgical treatment of internal hydrocephalus using ventriculoperitoneal shunts. Here we describe a case of a spontaneous hemispheric ventricular collapse in an untreated dog with congenital hydrocephalus internus. CASE PRESENTATION: A twelve-week-old, male, intact Golden Retriever was presented with a history of peracute obtundation, impaired vision, and progressive gait abnormalities of all limbs for three days. Neurological examination revealed a dome shaped skull, a broad-based stance and a moderate cerebellar ataxia. The postural responses were markedly delayed in all limbs. Moderate ventro-lateral strabismus, vertical nystagmus and absent menace response were observed bilaterally. Clinical signs indicated multifocal localisation (forebrain, cerebellum). Magnetic resonance imaging (MRI) showed dilation of all cerebral ventricles, irregular thinning of the periventricular white and grey matter, consistent with internal hydrocephalus. In addition, the hemispheres were collapsed at the right temporal and left frontal lobe with haemorrhage filling the adjacent subarachnoid space. The dog underwent left frontal and right temporal craniotomy for removal of the haemorrhage. The dog improved on all neurological signs and was discharged after seven days. A repeat MRI three months postsurgical intervention showed reexpansion of the cerebral hemispheres. Subarachnoid haemorrhages were markedly reduced. CONCLUSIONS: Collapse of the hemispheres can occur spontaneously in dogs with hydrocephalus internus. Removal of the haemorrhage can improve clinical signs.

Multiple cartilaginous exostoses in a Swiss Mountain dog causing thoracolumbar compressive myelopathy.

BACKGROUND: Multiple cartilaginous exostoses are a rare, benign, proliferative condition of cartilage and bone. They can be asymptomatic, or they may cause pain, lameness, paresis and even paralysis, depending on their location and size. In cases of spinal cord or nerve root compression, surgery is the treatment of choice. Therefore, an advanced imaging diagnostic work-up is indicated. Due to the unclear pathophysiology and progression of this condition, it is difficult to predict its prognosis. CASE PRESENTATION: A 9-month-old female Swiss Mountain dog was presented with a history of gait abnormalities, kyphosis and hypersensitivity consistent with a thoracolumbar myelopathy. Multiple calcified masses, most prominent at the Th7-Th9 level and the L2-L3 level, were observed. Magnetic resonance imaging of the thoracolumbar vertebral column revealed severe dorsal spinal cord compressions near the dorsal arch of the Th7-Th9 and L2-L3 vertebrae. Two of these masses were removed surgically. The successful removal of both masses was confirmed by postoperative computed tomography. The histopathological examination of the resected tissue revealed multiple cartilaginous exostoses. The first neurological and magnetic resonance follow up examination carried out 6 months postoperatively showed improvement of the clinical status. At that time, no mass regrowth was observed. The last follow up neurological examination carried out 15 months postoperatively showed gait improvement and resolution of pain. CONCLUSION: This is the first case report of multiple cartilaginous exostoses with a complete pre- and postoperative evaluation and a 15 month follow-up.

A practical technique to avoid the hippocampus in prophylactic cranial irradiation for lung cancer.

A practical technique is presented to deliver hippocampus avoiding prophylactic cranial irradiation for lung cancer patients, using two lateral fields. For a prescribed dose of 12×2.5 Gy, sparing of the hippocampi to 6.1 Gy was achieved with a V95% of the brain of 81.7%.

Fto immunoreactivity is widespread in the rodent brain and abundant in feeding-related sites, but the number of Fto-positive cells is not affected by changes in energy balance.

A single nucleotide polymorphism in the FTO gene is associated with obesity in humans. Evidence gathered in animals mainly relates energy homeostasis to the central FTO mRNA levels, but our knowledge of the Fto protein distribution and regulation is limited. Fto, a demethylase and transcriptional coactivator, is thought to regulate expression of other genes. Herein, we examined Fto immunoreactivity (IR) in the mouse and rat brain with emphasis on sites governing energy balance. We also studied whether energy status affects central Fto IR. We report that Fto IR, limited to nuclear profiles, is widespread in the brain, in- and outside feeding circuits; it shows a very similar distribution in feeding-related sites in mice and rats. Several areas regulating energy homeostasis display enhanced intensity of Fto staining: the arcuate, paraventricular, supraoptic, dorsomedial, ventromedial nuclei, and dorsal vagal complex. Some regions mediating feeding reward, including the bed nucleus of the stria terminalis, have ample Fto IR. We found that differences in energy status between rats fed ad libitum, deprived or refed following deprivation, did not affect the number of Fto-positive nuclei in 10 sites governing consumption for energy or reward. We conclude that Fto IR, widespread in the rodent brain, is particularly abundant in feeding circuits, but the number of Fto-positive neurons is unaffected by changes in energy balance.

Molecular, immunohistochemical, and pharmacological evidence of oxytocin's role as inhibitor of carbohydrate but not fat intake.

Oxytocin (OT) facilitates feeding termination stemming from high osmolality, stomach distention, and malaise. Recent knockout (KO) studies suggested a crucial function for OT in carbohydrate intake: OT-/- mice had increased preference for carbohydrates, including sucrose, but not fat (Intralipid). In striking contrast, sugar appetite was unaffected in the OT receptor KO mouse; data from wild-type animals have been insufficient. Therefore, we examined the involvement of OT in the regulation of sucrose vs. fat intake in C57BL/6 mice that served as a background KO strain. We exposed mice to a meal of sucrose or Intralipid and determined that the percentage of c-Fos-immunoreactive paraventricular hypothalamic OT neurons was elevated at termination of intake of either of the tastants, but this increase was 2-fold higher in sucrose-fed mice. A 48-h exposure to sucrose compared with Intralipid caused up-regulation of OT mRNA, whereas inherent individual preferences for sucrose vs. fat were not associated with differences in baseline OT expression as established with quantitative PCR. We found that L-368,899, an OT receptor antagonist, increased sugar intake when sucrose was presented alone or concurrently with Intralipid; it had no effect on Intralipid or total calorie consumption. L-368,899 affected Fos immunoreactivity in the paraventricular hypothalamus, arcuate nucleus, amygdala, and nucleus of the solitary tract, areas involved in aversion, satiety, and reward. This pattern serves as neuroanatomical basis of OT's complex role in food intake, including sucrose intake. The current findings expand our knowledge on OT and suggest that it acts as a carbohydrate-specific inhibitor of feeding.

Hypothalamic FTO is associated with the regulation of energy intake not feeding reward.

BACKGROUND: Polymorphism in the FTO gene is strongly associated with obesity, but little is known about the molecular bases of this relationship. We investigated whether hypothalamic FTO is involved in energy-dependent overconsumption of food. We determined FTO mRNA levels in rodent models of short- and long-term intake of palatable fat or sugar, deprivation, diet-induced increase in body weight, baseline preference for fat versus sugar as well as in same-weight animals differing in the inherent propensity to eat calories especially upon availability of diverse diets, using quantitative PCR. FTO gene expression was also studied in organotypic hypothalamic cultures treated with anorexigenic amino acid, leucine. In situ hybridization (ISH) was utilized to study FTO signal in reward- and hunger-related sites, colocalization with anorexigenic oxytocin, and c-Fos immunoreactivity in FTO cells at initiation and termination of a meal. RESULTS: Deprivation upregulated FTO mRNA, while leucine downregulated it. Consumption of palatable diets or macronutrient preference did not affect FTO expression. However, the propensity to ingest more energy without an effect on body weight was associated with lower FTO mRNA levels. We found that 4-fold higher number of FTO cells displayed c-Fos at meal termination as compared to initiation in the paraventricular and arcuate nuclei of re-fed mice. Moreover, ISH showed that FTO is present mainly in hunger-related sites and it shows a high degree of colocalization with anorexigenic oxytocin. CONCLUSION: We conclude that FTO mRNA is present mainly in sites related to hunger/satiation control; changes in hypothalamic FTO expression are associated with cues related to energy intake rather than feeding reward. In line with that, neurons involved in feeding termination express FTO. Interestingly, baseline FTO expression appears linked not only with energy intake but also energy metabolism.

The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain.

Gene variants of the FTO (fatso) gene have recently been strongly associated with body mass index and obesity. The FTO gene is well conserved and found in a single copy in vertebrate species including fish and chicken, suggesting that the ancestor of this gene was present 450 million years ago. Surprisingly, the FTO gene is present in two species of algae but not in any other invertebrate species. This could indicate that this gene has undergone a horizontal gene transfer. Quantitative real-time PCR showed that the gene is expressed in many peripheral and central rat tissues. Detailed in situ hybridization analysis in the mouse brain showed abundant expression in feeding-related nuclei of the brainstem and hypothalamus, such as the nucleus of the solitary tract, area postrema, and arcuate, paraventricular, and supraoptic nuclei as well as in the bed nucleus of the stria terminalis. Colabeling showed that the FTO gene is predominantly expressed in neurons, whereas it was virtually not found in astrocytes or glia cells. The FTO was significantly up-regulated (41%) in the hypothalamus of rats after 48-h food deprivation. We also found a strong negative correlation of the FTO expression level with the expression of orexigenic galanin-like peptide, which is mainly synthesized in the arcuate nucleus. These results are consistent with the hypothesis that FTO could participate in the central control of energy homeostasis.

Effect of angiotensin II on ANP-dependent guanylyl cyclase activity in cultured mouse and rat podocytes.

The presence of a well-developed contractile apparatus is the feature determining major roles of podocytes in the renal glomeruli. Receptors for a variety of vasoactive hormones are expressed in these cells; however, most of the signaling pathways are still unknown and remain to be elucidated. Angiotensin II (Ang II) and atrial natriuretic peptide (ANP), due to their opposite action, are the major modulators of glomerular filtration. In podocytes, Ang II induces rise in intracellular calcium concentration, whereas ANP stimulates generation of cGMP. The present study was designed to check whether ANP-stimulated cGMP synthesis in podocytes might be affected by Ang II. Cultured rat (RP) and mouse (MP) podocytes were stimulated with ANP, in the absence or presence of Ang II and cyclic GMP was determined by RIA method. Co-incubation of podocytes with ANP and Ang II caused significant (p < 0.01) suppression of ANP-dependent cGMP generation. The effect was prevented by saralasin, an inhibitor of angiotensin receptors. Phorbol-12-myristate-13-acetate (PMA) mimicked, whereas chelerythrine reversed inhibitory effect of Ang II. In conclusion, angiotensin II counteracts ANP-stimulated cGMP synthesis in cultured podocytes. It seems likely that the protein kinase C pathway is involved in this effect.