Development of Surgical Competence in Veterinary Students Using a Flipped Classroom Approach.

Clinical skills laboratory (CSL) training was recently introduced in the renewed veterinary curriculum at Ghent University, using models and simulators for teaching practical skills. However, time in the CSL is restricted due to the large number of students combined with limited availability of personnel. Therefore, a flipped classroom (FC) model was introduced to maximize learning experiences. The goal of the present study was to evaluate the effect of flipped classroom CSL training on students' self-efficacy and practical surgical skills. Flipped classroom CSL training was implemented for the third-year pre-clinical students (n = 196) in the 6-year veterinary medicine program. Prior to CSL sessions, students studied online 'learning paths,' including text, pictures, videos of the skills, links to background information, a forum, and a compulsory pre-class quiz. A pre- and post-test were administered before and after flipped classroom CSL training. The tests consisted of a self-efficacy scale consisting of 20 items and an objective structured clinical examination (OSCE) test of surgical skills performance. Flipped classroom CSL training resulted in significantly higher self-efficacy (score/100, pre-test 55 ± 14 vs. post-test 83 ± 8, p< .001) and surgical skills performance (score/20, pre-test 5 ± 3 vs. post-test 17 ± 3, p< .001). In conclusion, this study demonstrated the feasibility and value of implementing a flipped classroom approach in combination with CSL training.

Comparative pharmacokinetics of imepitoin after oral and rectal administration in healthy dogs.

The purpose of the present study was to investigate if rectal administration of imepitoin in healthy dogs leads to plasma concentrations comparable to those after oral administration. Significantly lower systemic exposure and maximal plasma concentration (Cmax) of imepitoin was achieved after rectal compared to oral administration (P≤0.001). Therefore, this study does not support the rectal administration of imepitoin in dogs.

Ammonia concentrations in arterial blood, venous blood, and cerebrospinal fluid of dogs with and without congenital extrahepatic portosystemic shunts.

OBJECTIVE To compare ammonia concentrations in arterial blood, venous blood, and CSF samples of dogs with and without extrahepatic portosystemic shunts (EHPSS). ANIMALS 19 dogs with congenital EHPSS and 6 healthy control dogs. PROCEDURES All dogs underwent a physical examination and then were anesthetized for transsplenic portal scintigraphy to confirm the presence or absence of EHPSS. While dogs were anesthetized, arterial and venous blood samples and a CSF sample were simultaneously collected for determination of ammonia concentration, which was measured by use of a portable blood ammonia analyzer (device A) and a nonportable biochemical analyzer (device B). Results were compared between dogs with EHPSS and control dogs. RESULTS Arterial, venous, and CSF ammonia concentrations for dogs with EHPSS were significantly greater than those for control dogs. For dogs with EHPSS, ammonia concentrations in both arterial and venous blood samples were markedly increased from the reference range. There was a strong positive correlation between arterial and venous ammonia concentrations and between blood (arterial or venous) and CSF ammonia concentrations. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that blood and CSF ammonia concentrations in dogs with EHPSS were greater than those for healthy dogs and were strongly and positively correlated, albeit in a nonlinear manner. This suggested that the permeability of the blood-brain barrier to ammonia may be abnormally increased in dogs with EHPSS, but further investigation of the relationship between blood or CSF ammonia concentration and clinical signs of hepatic encephalopathy or the surgical outcome for dogs with EHPSS is warranted.

Regional cerebral blood flow assessed by single photon emission computed tomography (SPECT) in dogs with congenital portosystemic shunt and hepatic encephalopathy.

Regional cerebral blood flow (rCBF) in eight dogs with congenital portosystemic shunt (PSS) and hepatic encephalopathy (HE) was compared with rCBF in eight healthy control dogs using single photon emission computed tomography (SPECT) with a 99mtechnetium-hexamethylpropylene amine oxime (99mTc-HMPAO) tracer. SPECT scans were abnormal in all PSS dogs. Compared to the control group, rCBF in PSS dogs was significantly decreased in the temporal lobes and increased in the subcortical (thalamic and striatal) area. Brain perfusion imaging alterations observed in the dogs with PSS and HE are similar to those in human patients with HE. These findings suggest that dogs with HE and PSS have altered perfusion of mainly the subcortical and the temporal regions of the brain.

Vagus Nerve Stimulator Placement in Dogs: Surgical Implantation Technique, Complications, Long-Term Follow-Up, and Practical Considerations.

OBJECTIVE: To describe a modified implantation procedure of a vagus nerve stimulation (VNS) device in dogs and to report short- and long-term complications. STUDY DESIGN: Descriptive, experimental study. ANIMALS: Healthy, adult Beagle dogs (n = 10). METHODS: A VNS Therapy(®) System was implanted in the left cervical region of anesthetized dogs. During and within 48 hours after surgery, electrocardiography (ECG) and impedance testing of the system were performed. Dogs were monitored daily and the impedance of the system was determined regularly until VNS devices were surgically removed 3 years after implantation. RESULTS: The implantation procedure was successful in all dogs without intraoperative complications. ECG monitoring and impedance tests were within normal limits during and within 48 hours after surgery. Postoperative seroma formation was common (70%). One dog developed an irreversible Horner's syndrome leading to removal of the device 5 months after implantation. Another dog developed trauma-induced damage of the lead requiring surgical revision. The device could be safely removed in all dogs; however, electrodes were left in place to avoid nerve damage. At removal, the anchor tether was dislodged in 40% of dogs and the lead was twisted in 50% of dogs. CONCLUSION: Implantation of a VNS Therapy(®) System is safe and feasible in dogs; however, seroma formation, twisting of the lead, and dislodgement of the anchor tether were common. Practical improvements in the technique include stable device placement, use of a compression bandage, and exercise restriction. Regular evaluation of lead impedance is important, as altered values can indicate serious complications.

A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever.

Alexander disease (AxD) is a fatal neurodegenerative disorder of astrocyte dysfunction in man, for which already a number of causal variants are described, mostly de novo dominant missense variants in the glial fibrillary acidic protein (GFAP). A similar disorder was already phenotypically described in animals but without the identification of causal variants. We diagnosed a Labrador retriever with a juvenile form of AxD based on clinical (tetraparesis with spastic front limbs mimicking 'swimming puppy syndrome') and pathological (the detection of GFAP containing Rosenthal fibers in astrocytes) features. In order to identify a causal variant, the coding sequences of the four detected GFAP transcript variants (orthologues from human transcript variants α, γ, δ/ɛ and κ) were sequenced. From the five detected variants, a heterozygous c.719G>A nucleotide substitution resulting in a p.Arg240His substitution was considered to be causal, because it is orthologous to the heterozygous de novo dominant c.716G>A (p.Arg239His) hotspot variant in man, proven to cause a severe phenotype. In addition, the variant was not found in 50 unrelated healthy Labrador retrievers. Because the condition in dogs is morphologically similar to man, it could be a promising animal model for further elucidating the genotype/phenotype correlation in order to treat or prevent this disease.

The effect of vagus nerve stimulation on CSF monoamines and the PTZ seizure threshold in dogs.

BACKGROUND: Vagus nerve stimulation (VNS) is an established treatment for refractory epilepsy in humans, but the precise mechanism of action (MOA), predictive responsive factors and the optimal stimulation parameters remain to be elucidated. OBJECTIVE: We aimed to investigate the effect of two rapid cycling VNS paradigms on CSF monoamine levels and the seizure threshold in the canine pentylenetetrazole (PTZ) model. METHODS: Eight Beagle dogs, implanted with a VNS Therapy(®) System, participated in a cross-over study. Levels of serotonin (5HT), norepinephrine (NE) and dopamine (DA) were quantified in the CSF after 1 h of sham, standard and microburst VNS with a wash-out period of 1 month. One week after the CSF experiment, the PTZ seizure threshold was determined after the same stimulation paradigm. As a positive control, the PTZ seizure threshold was determined after a single oral dose of phenobarbital. RESULTS: Rapid cycling standard and microburst VNS caused a significant increase of NE levels in the CSF (P = 0.03 and P = 0.02 respectively). No significant changes in 5HT or DA levels were detected. Rapid cycling standard and microburst VNS did not cause significant changes in the PTZ seizure threshold compared to sham. CONCLUSIONS: VNS induces an increase of NE in the canine brain, which supports previous findings indicating that VNS influences the locus coeruleus-NE (LC/NE) system. Importantly, this study demonstrates that this increase in NE is measurable in the CSF. One hour of VNS did not affect seizure threshold in the canine PTZ model. Therefore, the role of NE in the antiepileptic effect of VNS in dogs remains to be elucidated.

Evaluation of heart rate variability in dogs during standard and microburst vagus nerve stimulation: a pilot study.

Vagus nerve stimulation (VNS) is an established treatment for epilepsy and depression in human patients, but in both humans and dogs, optimal stimulation parameters remain unknown. Delivering afferent bursts of stimulation may be promising as a means of increasing efficacy, but evaluation of potential effects on the heart due to unavoidable efferent stimulation is required. The present study investigated heart rate variability (HRV) in healthy Beagle dogs treated with 1 h of sham, standard or microburst left-sided VNS in a crossover design. No significant differences were found between the stimulation paradigms for any of the cardiac parameters. Short-term left-sided VNS, including a novel bursting pattern (microburst VNS), had no statistically significant effect on HRV in ambulatory healthy dogs. Studies in a larger number of animals with long-term VNS are recommended.

Dominance of chemokine ligand 2 and matrix metalloproteinase-2 and -9 and suppression of pro-inflammatory cytokines in the epidural compartment after intervertebral disc extrusion in a canine model.

BACKGROUND CONTEXT: In canine intervertebral disc (IVD) disease, a useful animal model, only little is known about the inflammatory response in the epidural space. PURPOSE: To determine messenger RNA (mRNA) expressions of selected cytokines, chemokines, and matrix metalloproteinases (MMPs) qualitatively and semiquantitatively over the course of the disease and to correlate results to neurologic status and outcome. STUDY DESIGN/SETTING: Prospective study using extruded IVD material of dogs with thoracolumbar IVD extrusion. PATIENT SAMPLE: Seventy affected and 13 control (24 samples) dogs. OUTCOME MEASURES: Duration of neurologic signs, pretreatment, neurologic grade, severity of pain, and outcome were recorded. After diagnostic imaging, decompressive surgery was performed. METHODS: Messenger RNA expressions of interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF), interferon (IFN)γ, MMP-2, MMP-9, chemokine ligand (CCL)2, CCL3, and three housekeeping genes was determined in the collected epidural material by Panomics 2.0 QuantiGene Plex technology. Relative mRNA expression and fold changes were calculated. Relative mRNA expression was correlated statistically to clinical parameters. RESULTS: Fold changes of TNF, IL-1ß, IL-2, IL-4, IL-6, IL-10, IFNγ, and CCL3 were clearly downregulated in all stages of the disease. MMP-9 was downregulated in the acute stage and upregulated in the subacute and chronic phase. Interleukin-8 was upregulated in acute cases. MMP-2 showed mild and CCL2 strong upregulation over the whole course of the disease. In dogs with severe pain, CCL3 and IFNγ were significantly higher compared with dogs without pain (p=.017/.020). Dogs pretreated with nonsteroidal anti-inflammatory drugs revealed significantly lower mRNA expression of IL-8 (p=.017). CONCLUSIONS: The high CCL2 levels and upregulated MMPs combined with downregulated T-cell cytokines and suppressed pro-inflammatory genes in extruded canine disc material indicate that the epidural reaction is dominated by infiltrating monocytes differentiating into macrophages with tissue remodeling functions. These results will help to understand the pathogenic processes representing the basis for novel therapeutic approaches. The canine IVD disease model will be rewarding in this process.

Regional brain perfusion changes during standard and microburst vagus nerve stimulation in dogs.

PURPOSE: Vagus nerve stimulation (VNS) is an effective adjunctive treatment for refractory epilepsy in humans, but its mechanism of action (MOA) and optimal stimulation parameters are still unknown. Functional neuroimaging studies could provide better insight into the brain structures involved in the activity of VNS, but have not yet been described in dogs. The aim of this study was to investigate the effect of acute VNS on the regional cerebral blood flow (rCBF) in dogs using micro-SPECT (µ-SPECT). Additionally, a novel stimulation paradigm (microburst VNS) was used and compared with standard VNS. METHODS: A VNS Therapy System was implanted in ten Beagle dogs. µ-SPECT was performed after sham, standard and microburst VNS in a randomized, cross-over study. Nineteen volumes of interest (VOIs) were semi-quantitatively analysed and perfusion indices (PIs) were calculated. Furthermore, a rostro-caudal gradient (R-C), an asymmetry index (AI) and a cortical-subcortical index (Co-SCo) were determined. The SPECT results after standard and microburst VNS were compared pairwise with sham stimulation. RESULTS: Acute standard VNS did not cause significant rCBF alterations. Acute microburst VNS caused a significant hypoperfusion in the left frontal lobe (P=0.023) and in the right parietal lobe (P=0.035). Both stimulation paradigms did not cause changes in R-C, AI nor Co-SCo. CONCLUSIONS: Microburst VNS is more potent than standard VNS to modulate the rCBF in the dog. Our results promote further research towards the antiepileptic effect of microburst VNS in dogs and humans.

Non-pharmacological treatment options for refractory epilepsy: an overview of human treatment modalities and their potential utility in dogs.

Refractory epilepsy is a common disorder both in humans and dogs and treatment protocols are difficult to optimise. In humans, different non-pharmacological treatment modalities currently available include surgery, the ketogenic diet and neurostimulation. Surgery leads to freedom from seizures in 50-75% of patients, but requires strict patient selection. The ketogenic diet is indicated in severe childhood epilepsies, but efficacy is limited and long-term compliance can be problematic. In the past decade, various types of neurostimulation have emerged as promising treatment modalities for humans with refractory epilepsy. Currently, none of these treatment options are used in routine daily clinical practice to treat dogs with the condition. Since many dogs with poorly controlled seizures do not survive, the search for alternative treatment options for canine refractory epilepsy should be prioritised. This review provides an overview of non-pharmacological treatment options for human refractory epilepsy. The current knowledge and limitations of these treatments in canine refractory epilepsy is also discussed.

Idiopathic generalised tremor syndrome in two cats.

Two male neutered domestic shorthair cats were evaluated for generalised tremors. On neurological examination both cats showed whole-body tremors, worsening with stress. A mainly cerebellar disorder was suspected. Blood examination, cerebrospinal fluid analysis and electrophysiological examination of both cats and magnetic resonance imaging of the brain in one cat were normal. Idiopathic generalised tremor syndrome (IGTS) was suspected owing to the exclusion of underlying causes and the clinical similarities with the syndrome in dogs. Treatment as recommended for dogs was initiated and resulted in improvement. This report describes the first cases of IGTS in cats.

Myokymia and neuromyotonia in 37 Jack Russell terriers.

The clinical and clinicopathological characteristics, treatment and outcome of vermicular muscle contractions (myokymia) and generalized muscle stiffness (neuromyotonia) in 37 Jack Russell terriers were evaluated retrospectively. Thirty dogs were affected by both disorders, whereas seven were presented with myokymia and never developed neuromyotonia. Clinical signs started at the mean age of 8 months. Except for signs of myokymia and neuromyotonia, clinical and neurological examination was normal in all dogs. Thirty dogs demonstrated typical signs of hereditary ataxia. Changes in serum chemistry included increased creatine kinase, aspartate aminotransferase and alanine aminotransferase concentrations. Electromyographic abnormalities, especially in muscles showing macroscopically visible myokymia, consisted of semirhythmic bursts of doublet, triplet, or multiplet discharges of a single motor unit. The amplitudes varied between 80 µV and 1 mV and occurred with an interburst frequency between 10 and 40 Hz and an intraburst frequency between 150 and 280 Hz. Most dogs were treated with a sodium channel blocker with variable results. Seven dogs died (most likely because of hyperthermia) or were euthanased during a neuromyotonic attack; 15 dogs were euthanased due to worsening of clinical signs, or lack of or no long-lasting effect of medication, and three were euthanased for unknown or unrelated reasons. Nine dogs were lost to follow-up and three were still alive 5-10.5 years after the start of clinical signs. In conclusion, young Jack Russell terriers with myokymia and neuromyotonia should undergo a complete blood and electrophysiological examination. Long-term prognosis is not favourable.

Regional brain perfusion in epileptic dogs evaluated by technetium-99m-ethyl cysteinate dimer SPECT.

We evaluated the feasibility of interictal single photon emission computed tomography (SPECT) to detect alterations in regional cerebral blood flow and neuronal activity in dogs with idiopathic epilepsy. Twelve dogs with idiopathic epilepsy underwent interictal technetium-99m-ethyl cysteinate dimer SPECT of the brain. Different cortical regions of interest (ROIs), 1 ROI at the cerebellum and 1 ROI at the subcortical area were evaluated by semiquantitative analysis and compared with a control group (18 dogs). Significant hypoperfusion (P = 0.02) was present in the subcortical area of epileptic dogs. This hypoperfusion was not associated with seizure frequency, age at onset of seizures, duration of epilepsy, or time since the last seizure. Interictal SPECT did not reveal cortical or cerebellar perfusion alterations. The subcortical area may play an important role in the pathophysiology of canine idiopathic epilepsy.

Surgical treatment of a canine intranasal meningoencephalocele.

OBJECTIVE: To report the clinical signs, diagnosis, and surgical treatment of an intranasal meningoencephalocele in a dog. STUDY DESIGN: Case report. ANIMAL: Female Border collie, 5 months old. METHODS: A right intranasal meningoencephalocele was identified by computed tomography and magnetic resonance imaging. RESULTS: The lesion was approached by a modified transfrontal craniotomy. Surgical closure of the defect at the level of the cribriform plate and removal of extruded brain tissue resulted in regression of lacrimation and coincided with absence of seizuring. Treatment with phenobarbital was gradually reduced and stopped at 7 months after surgery. At 28 months the dog remained free of seizures. CONCLUSION: Meningoencephalocele, although rare, can cause seizures in dogs and can be treated surgically. CLINICAL RELEVANCE: A transfrontal craniotomy with excision of the meningoencephalocele and closure of the defect can be an effective treatment for an intranasal meningoencephalocele in dogs.

Magnetic stimulation of the radial nerve in dogs and cats with brachial plexus trauma: a report of 53 cases.

Brachial plexus trauma is a common clinical entity in small animal practice and prognostic indicators are essential early in the course of the disease. Magnetic stimulation of the radial nerve and consequent recording of the magnetic motor evoked potential (MMEP) was examined in 36 dogs and 17 cats with unilateral brachial plexus trauma. Absence of deep pain perception (DPP), ipsilateral loss of panniculus reflex, partial Horner's syndrome and a poor response to MMEP were related to the clinical outcome in 29 of the dogs and 13 of the cats. For all animals, a significant difference was found in MMEP between the normal and the affected limb. Absence of DPP and unilateral loss of the panniculus reflex were indicative of an unsuccessful outcome in dogs. Additionally, the inability to evoke a MMEP was associated with an unsuccessful outcome in all animals. It was concluded that magnetic stimulation of the radial nerve in dogs and cats with brachial plexus trauma may provide an additional diagnostic and prognostic tool.