Pharmacokinetics of rectal levetiracetam as add-on treatment in dogs affected by cluster seizures or status epilepticus.

BACKGROUND: Levetiracetam can be used for seizure control alone or in combination with other antiepileptic medications. A previous study achieved the minimum targeted serum drug concentration after rectal administration of levetiracetam in healthy dogs. The purpose of the present study was to determine the pharmacokinetics of rectal LEV in dogs presented for cluster seizures or status epilepticus and potentially in treatment with other anti-epileptic drugs. Furthermore, preliminary information on response to this treatment as add-on to the standard treatment protocol is reported. RESULTS: Eight client-owned dogs were enrolled. Plasma levetiracetam concentrations (measured at 0, 30, 60, 90, 120, 180, 240, 360, 720, and 1440 min after drug administration) reached the minimum target concentration (5 µg/ml) at 30 min in all but one patient. At T1 (30 min) the mean concentration was 28.2 ± 15.5 µg/ml. Plasma concentrations remained above the targeted minimum concentration in all patients until 240 min and in 7/8 until 360 min. Six out of eight patients experienced no seizures in the 24-h period after hospitalization and were classified as "responders". CONCLUSIONS: Minimum plasma levetiracetam concentration can be reached after rectal administration of 40 mg/kg in dogs affected by cluster seizures and status epilepticus and concurrently receiving other antiepileptic drugs. These preliminary results may encourage the evaluation of rectal levetiracetam as an additional treatment option for cluster seizures and status epilepticus in a larger number of dogs.

Neuronal ceroid lipofuscinosis associated with an MFSD8 mutation in Chihuahuas.

The neuronal ceroid lipofuscinoses (NCLs) are hereditary neurodegenerative disorders characterized by progressive declines in neurological functions, seizures, and premature death. NCLs result from mutations in at least 13 different genes. Canine versions of the NCLs can serve as important models in developing effective therapeutic interventions for these diseases. NCLs have been described in a number of dog breeds, including Chihuahuas. Studies were undertaken to further characterize the pathology of Chihuahua NCL and to verify its molecular genetic basis. Four unrelated client owned Chihuahuas from Japan, Italy and England that exhibited progressive neurological signs consistent with a diagnosis of NCL underwent neurological examinations. Brain and in some cases also retinal and heart tissues were examined postmortem for the presence of lysosomal storage bodies characteristic of NCL. The affected dogs exhibited massive accumulation of autofluorescent lysosomal storage bodies in the brain, retina and heart accompanied by brain atrophy and retinal degeneration. The dogs were screened for known canine NCL mutations previously reported in a variety of dog breeds. All 4 dogs were homozygous for the MFSD8 single base pair deletion (MFSD8:c.843delT) previously associated with NCL in a Chinese Crested dog and in 2 affected littermate Chihuahuas from Scotland. The dogs were all homozygous for the normal alleles at the other genetic loci known to cause different forms of canine NCL. The MFSD8:c.843delT mutation was not present in 57 Chihuahuas that were either clinically normal or suffered from unrelated diseases or in 1761 unaffected dogs representing 186 other breeds. Based on these data it is almost certain that the MFSD8:c.843delT mutation is the cause of NCL in Chihuahuas. Because the disorder occurred in widely separated geographic locations or in unrelated dogs from the same country, it is likely that the mutant allele is widespread among Chihuahuas. Genetic testing for this mutation in other Chihuahuas is therefore likely to identify intact dogs with the mutant allele that could be used to establish a research colony that could be used to test potential therapeutic interventions for the corresponding human disease.

Assessing lung consolidation in goats using different ultrasonographic techniques.

Goats are often affected by respiratory diseases and, despite ultrasonography can assess lung consolidations in several species, it is rarely used in these animals. So, this study evaluated the effectiveness of on-farm lung ultrasonography in detecting lung consolidations on 27 goats. The goats, scheduled for slaughter, underwent complete clinical examinations and lung ultrasonography. For the latter, both sides of the thorax were divided in four quadrants and examined using convex and linear probes before and after shaving the hair. Each quadrant was classified based on presence/absence of lung consolidation and maximum consolidation's depth (4-point scale: 0 healthy; 1 depth < 1 cm; 2 depth < 3 cm; 3 depth > 3 cm). The lungs were examined at necropsy, 66% of goats exhibited lung consolidations and sensitivity (83%-89%), specificity (100%), and κ coefficient values (0.67-0.72) were high with all techniques. An higher (p ≤ 0.01) percentage of class 1 lesions were found at necropsy compared to all the ultrasonographic techniques. All the ultrasonographic techniques effectively detected lung consolidation deeper than 1 cm. So, ultrasonography seems an effective tool for lung examination in goats with chronic pneumonia. The examination using the linear or the convex probes without shaving the hair could be a promising tool for the on-field diagnosis of pneumonia, although further research on larger sample sizes are necessary to validate these findings.

Changes in glial cell activation and extracellular vesicles production precede the onset of disease symptoms in transgenic hSOD1G93A pigs.

SOD1 gene is associated with progressive motor neuron degeneration in the familiar forms of amyotrophic lateral sclerosis. Although studies on mutant human SOD1 transgenic rodent models have provided important insights into disease pathogenesis, they have not led to the discovery of early biomarkers or effective therapies in human disease. The recent generation of a transgenic swine model expressing the human pathological hSOD1G93A gene, which recapitulates the course of human disease, represents an interesting tool for the identification of early disease mechanisms and diagnostic biomarkers. Here, we analyze the activation state of CNS cells in transgenic pigs during the disease course and investigate whether changes in neuronal and glial cell activation state can be reflected by the amount of extracellular vesicles they release in biological fluids. To assess the activation state of neural cells, we performed a biochemical characterization of neurons and glial cells in the spinal cords of hSOD1G93A pigs during the disease course. Quantification of EVs of CNS cell origin was performed in cerebrospinal fluid and plasma of transgenic pigs at different disease stages by Western blot and peptide microarray analyses. We report an early activation of oligodendrocytes in hSOD1G93A transgenic tissue followed by astrocyte and microglia activation, especially in animals with motor symptoms. At late asymptomatic stage, EV production from astrocytes and microglia is increased in the cerebrospinal fluid, but not in the plasma, of transgenic pigs reflecting donor cell activation in the spinal cord. Estimation of EV production by biochemical analyses is corroborated by direct quantification of neuron- and microglia-derived EVs in the cerebrospinal fluid by a Membrane Sensing Peptide enabled on-chip analysis that provides fast results and low sample consumption. Collectively, our data indicate that alteration in astrocytic EV production precedes the onset of disease symptoms in the hSODG93A swine model, mirroring donor cell activation in the spinal cord, and suggest that EV measurements from the cells first activated in the ALS pig model, i.e. OPCs, may further improve early disease detection.

Ocular Ultrasonography in Healthy Calves with Different Transducers.

Ocular ultrasonography is seldom performed in cattle. Here, we compared three ultrasound probes (linear, convex, transrectal gynecological) for the measurement of eight eye biometry parameters on vertical and horizontal scans. The sample population was 20 healthy calves (n = 10 Holstein, n = 10 Piedmontese breed). Intragroup (same probe for vertical vs. horizontal scanning) and intergroup (different probes measuring the same biometric parameter) comparisons were performed using Student's t-test and the Mann-Whitney U test. Statistical significance was set at p ≤ 0.05. Intragroup comparison revealed few significant differences. Ultrasound examination with the convex transducer detected more differences than either of the two other probes on vertical (linear six out of eight; transrectal gynecological four out of eight) and horizontal (linear six out of eight; transrectal gynecological six out of eight) scans. Similar results were obtained for both breeds. More non-valuable parameters on the horizontal (77 out of 320, 24%) and the vertical (85 out of 320, 26%) (p ≤ 0.001) scans were obtained with the convex transducer. Both linear transducers were found comparable for ocular ultrasonography in field conditions. However, given its widespread application in the field, the transrectal gynecological transducer may offer veterinarians the added advantage of familiarity and ease-of-use without any additional costs.

Duration of constant rate infusion with diazepam or propofol for canine cluster seizures and status epilepticus.

Introduction: Constant rate infusion (CRI) of benzodiazepines or propofol (PPF) is a therapeutic option for cluster seizures (CS) and status epilepticus (SE) in canine patients non-responding to first-line benzodiazepines or non-anesthetics. However, specific indications for optimal duration of CRI are lacking. The aim of this study was to determine the effect of duration of anesthetic CRI on outcome and length of hospital stay in dogs with refractory seizure activity of different etiology. Study design: Open-label non-randomized clinical trial. Materials and methods: Seventy-three client-owned dogs were enrolled. Two groups [experimental (EXP) vs. control (CTRL)] were compared. The EXP group received diazepam (DZP) or PPF CRI for 12 h (±1 h) and the CTRL group received DZP or PPF CRI for 24 h (±1 h) in addition to a standardized emergency treatment protocol identical for both study groups. The historical control group was made up of a population of dogs already reported in a previously published paper by the same authors. Favorable outcome was defined as seizure cessation after CRI, no seizure recurrence, and clinical recovery. Poor outcome was defined as seizure recurrence, death in hospital or no return to acceptable clinical baseline. Univariate statistical analysis was performed. Results: The study sample was 73 dogs: 45 (62%) received DZP CRI and 28 (38%) received PPF CRI. The EXP group was 39 dogs (25 DZP CRI and 14 PPF CRI) and the CTRL group 34 dogs (20 DZP CRI and 14 PPF CRI). We found no statistically significant difference in outcomes between the groups. The median length of stay was 56 h (IQR, 40-78) for the ALL EXP group and 58.5 h (IQR, 48-74.5) for the ALL CTRL group (p = 0.8). Conclusion: Even though a shorter DZP or PPF CRI duration was not associated with a worse outcome, the study failed to identify a clear superiority of shorter CRI duration on outcome or length of hospital stay in dogs with refractory seizure activity of different etiology.

Feasibility of 16S rRNA sequencing for cerebrospinal fluid microbiome analysis in cattle with neurological disorders: a pilot study.

Bacterial infection of the central nervous system (CNS) in cattle requires prompt and adequate antimicrobial treatment. The current gold standard for antemortem etiological diagnosis is cerebrospinal fluid (CSF) culture, which often yields false negative results. CSF has long been considered a sterile district in healthy patients, but this notion has been recently challenged. For this pilot study, we used 16S rRNA gene sequencing to investigate the microbial composition of CSF of cattle presenting with CNS disorders and to compare it between subjects with CNS infections and with CNS disorders of other nature. The study sample was 10 animals: 4 presenting with CNS infectious-inflammatory diseases and 6 with other CNS disorders, based on definitive diagnosis. Since the initial round of a standard 16S rRNA PCR did not yield sufficient genetic material for sequencing in any of the samples, the protocol was modified to increase its sensitivity. Bacterial genetic material was identified in 6 animals and 2 groups were formed: an infectious inflammatory (n = 3) and a noninfectious inflammatory group (n = 3). The most frequently expressed bacterial families were Pseudomonadaceae (44.61%), Moraxellaceae (19.54%), Mycobacteriaceae (11.80%); the genera were Pseudomonas (45.42%), Acinetobacter (19.91%), Mycobacterium (12.01%). There were no detectable differences in the CSF microbial composition of the samples from the two groups. Sequencing of bacterial DNA present in the CSF was possible only after increasing PCR sensitivity. The results of 16S rRNA sequencing showed the presence of a microbial community in the CSF in cattle with neurological disorders. Further studies, in which CSF samples from healthy animals and samples from the environment are included as controls, are needed.

A novel machine learning-based web application for field identification of infectious and inflammatory disorders of the central nervous system in cattle.

BACKGROUND: Central nervous system (CNS) infections in cattle are a major cause of economic loss and mortality. Machine learning (ML) techniques are gaining widespread application in solving predictive tasks in both human and veterinary medicine. OBJECTIVES: Our primary aim was to develop and compare ML models that could predict the likelihood of a CNS disorder of infectious or inflammatory origin in neurologically-impaired cattle. Our secondary aim was to create a user-friendly web application based on the ML model for the diagnosis of infection and inflammation of the CNS. ANIMALS: Ninety-eight cattle with CNS infection and 86 with CNS disorders of other origin. METHODS: Retrospective observational study. Six different ML methods (logistic regression [LR]; support vector machine [SVM]; random forest [RF]; multilayer perceptron [MLP]; K-nearest neighbors [KNN]; gradient boosting [GB]) were compared for their ability to predict whether an infectious or inflammatory disease was present based on demographics, neurological examination findings, and cerebrospinal fluid (CSF) analysis. RESULTS: All 6 methods had high prediction accuracy (≥80%). The accuracy of the LR model was significantly higher (0.843 ± 0.005; receiver operating characteristic [ROC] curve 0.907 ± 0.005 ) than the other models and was selected for implementation in a web application. CONCLUSION AND CLINICAL IMPORTANCE: Our findings support the use of ML algorithms as promising tools for veterinarians to improve diagnosis. The open-access web application may aid clinicians in achieving correct diagnosis of infectious and inflammatory neurological disorders in livestock, with the added benefit of promoting appropriate use of antimicrobials.

Brain-Derived Neurotrophic Factor, Kynurenine Pathway, and Lipid-Profiling Alterations as Potential Animal Welfare Indicators in Dairy Cattle.

Complete animal welfare evaluation in intensive farming is challenging. With this study, we investigate new biomarkers for animal physical and mental health by comparing plasma expression of biochemical indicators in dairy cows reared in three different systems: (A) semi-intensive free-stall, (B) non-intensive tie-stall, and (C) intensive free-stall. Additionally, protein levels of mature brain-derived neurotrophic factor (mBDNF) and its precursor form (proBDNF) and indoleamine 2,3-dioxygenase (IDO1) specific activity were evaluated in brain samples collected from 12 cattle culled between 73 and 138 months of age. Alterations in plasma lipid composition and in the kynurenine pathway of tryptophan metabolism were observed in the tie-stall-reared animals. The total plasma BDNF concentration was higher in tie-stall group compared to the two free-housing groups. Brain analysis of the tie-stall animals revealed a different mBDNF/proBDNF ratio, with a higher level of proBDNF (p < 0.001). Our data are similar to previous studies on animal models of depression, which reported that inhibition of the conversion of proBDNF in its mature form and/or elevated peripheral kynurenine pathway activation may underlie cerebral biochemical changes and induce depressive-like state behavior in animals.

Constant rate infusion of diazepam or propofol for the management of canine cluster seizures or status epilepticus.

Introduction: Cluster seizures (CS) and status epilepticus (SE) in dogs are severe neurological emergencies that require immediate treatment. Practical guidelines call for constant rate infusion (CRI) of benzodiazepines or propofol (PPF) in patients with seizures not responding to first-line treatment, but to date only few studies have investigated the use of CRI in dogs with epilepsy. Study design: Retrospective clinical study. Methods: Dogs that received CRI of diazepam (DZP) or PPF for antiepileptic treatment during hospitalization at the Veterinary Teaching Hospital of the University of Turin for CS or SE between September 2016 and December 2019 were eligible for inclusion. Favorable outcome was defined as cessation of clinically visible seizure activity within few minutes from the initiation of the CRI, no seizure recurrence within 24 h after discontinuation of CRI through to hospital discharge, and clinical recovery. Poor outcome was defined as recurrence of seizure activity despite treatment or death in hospital because of recurrent seizures, catastrophic consequences of prolonged seizures or no return to an acceptable neurological and clinical baseline, despite apparent control of seizure activity. Comparisons between the number of patients with favorable outcome and those with poor outcome in relation to type of CRI, seizure etiology, reason for presentation (CS or SE), sex, previous AED therapy and dose of PPF CRI were carried out. Results: A total of 37 dogs, with 50 instances of hospitalization and CRI administered for CS or SE were included in the study. CRI of diazepam (DZP) or PPF was administered in 29/50 (58%) and in 21/50 (42%) instances of hospitalization, respectively. Idiopathic epilepsy was diagnosed in 21/37 (57%), (13/21 tier I and 8/21 tier II); structural epilepsy was diagnosed in 6/37 (16%) of which 4/6 confirmed and 2/6 suspected. A metabolic or toxic cause of seizure activity was recorded in 7/37 (19%). A total of 38/50 (76%) hospitalizations were noted for CS and 12/50 (24%) for SE. In 30/50 (60%) instances of hospitalization, the patient responded well to CRI with cessation of seizure activity, no recurrence in the 24 h after discontinuation of CRI through to hospital discharge, whereas a poor outcome was recorded for 20/50 (40%) cases (DZP CRI in 12/50 and PPF CRI in 8/50). Comparison between the number of patients with favorable outcome and those with poor outcome in relation to type of CRI, seizure etiology, reason for presentation (CS or SE), sex and previous AED therapy was carried out but no statistically significant differences were found. Conclusions: The present study is the first to document administration of CRI of DZP or PPF in a large sample of dogs with epilepsy. The medications appeared to be tolerated without major side effects and helped control seizure activity in most patients regardless of seizure etiology. Further studies are needed to evaluate the effects of CRI duration on outcome and complications.

A Retrospective, Observational Study on Antimicrobial Drug Use in Beef Fattening Operations in Northwestern Italy and Evaluation of Risk Factors Associated with Increased Antimicrobial Usage.

The abuse or misuse of antimicrobials in animal production is thought to be a potential factor in the development of antimicrobial resistance in veterinary and human medicine. With this study, we wanted to quantify antimicrobial usage in beef fattening operations in northwestern Italy and to identify factors potentially influencing antimicrobial usage. The sample was composed of 26 beef fattening operations that import heifers and bulls from France. Data were extracted from the 2014 and 2015 treatment registers kept by the farmers. The mean (±SD) number of animal daily doses per animal (nADDa) per year for each farm was 3 (±2.1) during the study period (2014-2015). Group antimicrobial treatments (57.5% of all treatments) were often administered orally (70.5%) and consisted overwhelmingly of doxycycline (97%). Individual treatments (42.5% of all treatments) were administered parenterally (98.1%) and the most often used active substances were florfenicol (19.9%), marbofloxacin (19.5%), and tylosin (12.4%). There was a negative correlation between the nADDa for total and group treatments and average batch weight at arrival and between the amount of straw added per animal per day and the nADDa (p ≤ 0.05). Our data show that antimicrobials critical for human medicine were often used in beef fattening operations in northwestern Italy before the European guidelines for the prudent use of antimicrobials in veterinary medicine were issued. Additionally, the use of antimicrobials as a preventive group treatment was still widespread, mostly in lighter weight animals.

RT-QuIC detection of pathological prion protein in subclinical goats following experimental oral transmission of L-type BSE.

OBJECTIVE: The spread of bovine spongiform encephalopathy (BSE) agent to small ruminants is still a major issue in the surveillance of transmissible spongiform encephalopathies (TSEs). L-type bovine spongiform encephalopathy (L-BSE) is an atypical form of BSE with an unknown zoonotic potential that is transmissible to cattle and small ruminants. Our current knowledge of bovine atypical prion strains in sheep and goat relies only on experimental transmission studies by intracranial inoculation. To assess oral susceptibility of goats to L-BSE, we orally inoculated five goats with cattle L-BSE brain homogenates and investigated pathogenic prion protein (PrPsc) distribution by an ultrasensitive in vitro conversion assay known as Real-Time Quaking Induced Conversion (RT-QuIC). RESULTS: Despite a prolonged observation period of 80 months, all these animals and the uninfected controls did not develop clinical signs referable to TSEs and tested negative by standard diagnostics. Otherwise, RT-QuIC analysis showed seeding activity in five out of five examined brain samples. PrPsc accumulation was also detected in spinal cord and lymphoreticular system. These results indicate that caprine species are susceptible to L-BSE by oral transmission and that ultrasensitive prion tests deserve consideration to improve the potential of current surveillance systems against otherwise undetectable forms of animal prion infections.

Spinal Muscular Atrophy in Blonde D'Aquitaine Calves Is Not Associated With FVT1 Gene Mutation.

Spinal muscular atrophy (SMA) is a motor neuron disease (MND) in humans and diverse animal species: canid, felid, and bovid. To date, bovine SMA has been reported in Brown Swiss, Holstein, Friesian, and Red Danish breed; it has been associated with a genetic mutation of the FVT1 gene, also known as 3-ketodihydrosphingosine reductase (KDSR). The aim of the present case series was to describe clinical presentation, pathological findings, and genetic analysis of five Blond d'Aquitaine calves diagnosed with SMA and to determine whether the mutation was associated with the disease. Five Blonde d'Aquitaine calves (three females and two males) from the same cow-calf operation farm were presented between June 2018 and February 2019 because unable to stand or walk unassisted since birth. Neurological examination aroused suspicion of a diffuse lesion affecting the peripheral nervous system in all calves. Findings from electromyographic investigations and muscle and nerve biopsies were consistent with a non-regenerative, chronic, active axonal neuropathy and marked neurogenic muscular atrophy and assumed to be associated with a neurodegenerative process. Histopathological examination of tissue samples from two animals revealed neuronal loss and several degenerated, shrunken, and hypereosinophilic neurons at the level of the ventral horn of the cervico-thoracic and the lumbo-sacral intumescence, diffuse loss of myelinated axons at the level of the ventral funiculi of all segments of the spinal cord, and moderate diffuse astrocytic reaction. These findings confirmed the diagnosis of SMA. No mutation of the FVT1 gene was found on genetic analysis. Further study into the causative gene mutation of SMA in Blonde D'Aquitaine calves is under way. Identification of a novel genetic mutation could improve our understanding of the disease in human medicine.

Upper digestive tract abnormalities in dogs with chronic idiopathic lymphoplasmacytic rhinitis.

BACKGROUND: Chronic idiopathic lymphoplasmacytic rhinitis (CILPR) is a common inflammatory disorder of unknown etiology affecting the nasal cavity of dogs. The diagnosis is made by exclusion of other causes of nasal disease and specific therapeutic protocols are lacking. In human medicine, a relationship between CILPR and gastrointestinal clinical signs has been postulated, and remission of respiratory signs after clinical trials with medications for gastrointestinal disorders has been observed. OBJECTIVES: To describe history, clinical presentation, endoscopic and histopathologic concurrent respiratory and digestive tract abnormalities, and to evaluate improvement of respiratory signs after treatment for gastrointestinal signs. ANIMALS: Twenty-five dogs with CILPR. METHODS: Prospective study. For inclusion, following information had to be available: respiratory and digestive clinical signs, airway and digestive tract endoscopic abnormalities, histologic evaluation of respiratory and gastrointestinal tract biopsy specimens, and clinical response to different treatment strategies. RESULTS: Twenty-two dogs had endoscopic gastrointestinal lesions, whereas 13 dogs had concurrent gastrointestinal signs. Most esophageal and duodenal endoscopic abnormalities were classified as moderate or severe. Respiratory and gastrointestinal tract histologic evaluation identified mostly chronic inflammation. Remission or marked improvement of respiratory signs was observed in the majority of dogs treated only for gastrointestinal signs up to 12 months after endoscopy. No significant associations between treatments and follow-up information were found. CONCLUSION AND CLINICAL IMPORTANCE: Nasal and upper digestive tract abnormalities coexist in some dogs with CILPR. Lack of standardized therapeutic protocols suggests caution when interpreting improvement in nasal clinical signs. Additional studies are needed to explore the possibility of a cause-effect relationship between the 2 processes.

Behavioral Therapy and Fluoxetine Treatment in Aggressive Dogs: A Case Study.

Canine aggression is a major concern, affecting millions of people worldwide, and treatment can be challenging even for skilled veterinarians. Empiric use of fluoxetine is sometimes attempted, although few data regarding long-term effects in aggressive dogs are available. The aim of the study was to investigate clinical effectiveness of fluoxetine (1.5 mg/kg/die PO) combined with a behavior modification program for treatment of canine dominance-related aggression. Circulating levels of fluoxetine, norfluoxetine, and serotonin (5-HT) were also measured. Eight dogs with a diagnosis of dominance aggression (owner-directed) were enrolled. Before treatment (T0), and after one (T1), two (T2), four (T3), and six (T4) months of fluoxetine administration, clinical outcomes were graded using a five-point frequency scale (0-4), and blood samples were collected to measure fluoxetine/norfluoxetine (high-performance liquid chromatography) and 5-HT (ELISA) levels. Following treatment, a decrease in behavioral test scores was observed at T1-T4. Increasing concentrations of circulating fluoxetine and norfluoxetine were measured throughout the follow-up. Correlation between norfluoxetine levels and clinical scores was observed at T4. Starting from T1, a significant decrease in 5-HT levels was observed. Our data suggest that fluoxetine (1.5 mg/kg/day) when associated with behavior treatment is effective in controlling canine aggression over a six-month period, and that, in dogs norfluoxetine levels seem reliable in predicting clinical efficacy.

Analysis of Early Assessable Risk Factors for Poor Outcome in Dogs With Cluster Seizures and Status Epilepticus.

Status epileptics (SE) and cluster seizures (CS) are serious neurological emergencies associated with poor outcome in epileptic patients. Data on risk factors associated with outcome in epileptic patients affected by CS and SE have not been studied extensively to date. In the present retrospective study potential risk factors predictive of negative outcome in a population of dogs affected by CS and SE were analyzed. Ninety-three dogs were included in the study: 21/93 patients (23%) presented with SE and 72/93 (77%) with CS. Based on multivariate statistical analysis, factors statistically associated with a poor outcome were the occurrence of the first epileptic seizure outside the defined idiopathic interval (6 months-6 years), a condition of hyperthermia at presentation and the absence of previous antiepileptic drugs (AEDs) in case of previous history of seizures. The results of the present study implement data on risk factors associated with poor outcome in dogs affected by CS or SE and can aid in the creation of an ad hoc scoring system, similar to systems currently applied in human medicine upon hospital admission to benchmark performances and establish protocols for triage and therapeutic management.

Imaging and genetic investigations of neural tube defect in a calf: case report and review of the literature.

A 15-d-old female crossbreed calf was referred because of paraplegia since birth. Clinical examination revealed a skin defect covered by hair on the dorsal midline in the thoracic area of the spine. Thoracolumbar spinal cord neuroanatomic localization was determined based on neurologic examination. Computed tomography of the thoracolumbar spine revealed incomplete fusion of the vertebral arches from T6 to T10 and duplication of the vertebral arch of T7. At the level of T6-T7, duplication of the spinal cord with 2 segments completely separated by a septum of hyperattenuating, probably cartilaginous, tissue was noted. Histologically, the spinal segments had different degrees of duplication. Three central canals were detected in one region. Genetic investigation for the presence of methylenetetrahydrofolate reductase (MTHFR) polymorphism, which has been investigated in both human and veterinary medicine as a possible cause of neural tube defects and abortion, was carried out and was negative in both the calf and her dam.

Open-label clinical trial of rectally administered levetiracetam as supplemental treatment in dogs with cluster seizures.

BACKGROUND: Treatment options for at-home management of cluster seizures (CS) and status epilepticus (SE) are limited. The pharmacokinetics of levetiracetam (LEV) after rectal administration in both healthy and epileptic dogs has been investigated recently. HYPOTHESIS/OBJECTIVES: To investigate the clinical efficacy of rectally administered LEV in preventing additional seizures in dogs presented for CS and SE. We hypothesized that rectal administration of LEV in addition to a standard treatment protocol would provide better control of seizure activity as compared with the standard treatment protocol alone. ANIMALS: Fifty-seven client-owned dogs with CS or SE. METHODS: Prospective open-label clinical trial. Patients included in the study were assigned to receive either a standard treatment protocol comprising IV/rectal diazepam and IV phenobarbital q8h (control group) or a standard treatment protocol in association with a single dose of 40 mg/kg LEV rectally (rectal LEV group). Dogs that experienced no additional seizures were defined as responders, whereas those that showed additional seizure activity were classified as nonresponders. RESULTS: Twenty-one dogs were assigned to the rectal LEV group, and 36 to control group. Given the small number of cases of SE, statistical analysis was performed only on patients with CS. The response rate was 94% in the rectal LEV group and 48% in the control group (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Rectally administered LEV combined with a standard treatment protocol provided good control of seizure activity in patients with CS. The validity of these results should be confirmed in a double-blinded, placebo-controlled clinical trial.