Pregabalin Add-On vs. Dose Increase in Levetiracetam Add-On Treatment: A Real-Life Trial in Dogs With Drug-Resistant Epilepsy.

Epilepsy is a common neurological disorder affecting 0.6-0.75% of dogs in veterinary practice. Treatment is frequently complicated by the occurrence of drug-resistant epilepsy and cluster seizures in dogs with idiopathic epilepsy. Only few studies are available to guide treatment choices beyond licensed veterinary drugs. The aim of the study was to compare antiseizure efficacy and tolerability of two add-on treatment strategies in dogs with drug-resistant idiopathic epilepsy. The study design was a prospective, open-label, non-blinded, comparative treatment trial. Treatment success was defined as a 3-fold extension of the longest baseline interseizure interval and to a minimum of 3 months. To avoid prolonged adherence to a presumably ineffective treatment strategy, dog owners could leave the study after the third day with generalized seizures if the interseizure interval failed to show a relevant increase. Twenty-six dogs (mean age 5.5 years, mean seizure frequency 4/month) with drug-resistant idiopathic epilepsy and a history of cluster seizures were included. Dogs received either add-on treatment with pregabalin (PGB) 4 mg/kg twice daily (14 dogs) or a dose increase in levetiracetam (LEV) add-on treatment (12 dogs). Thirteen dogs in the PGB group had drug levels within the therapeutic range for humans. Two dogs in the PGB group (14.3%; 2/14) and one dog in the LEV group (8.3%; 1/12) achieved treatment success with long seizure-free intervals from 122 to 219 days but then relapsed to their early seizure frequency 10 months after the study inclusion. The overall low success rates with both treatment strategies likely reflect a real-life situation in canine drug-resistant idiopathic epilepsy in everyday veterinary practice. These results delineate the need for research on better pharmacologic and non-pharmacologic treatment strategies in dogs with drug-resistant epilepsy.

[Trichinella induced polymyositis with unilateral lameness in a dog]. / Polymyositis mit einseitiger Lahmheit im Rahmen einer Trichinellose beim Hund.

A 9-year-old Cairn Terrier was presented for a right thoracic limb lameness of 3-month duration resistant to anti-inflammatory pain treatment. Blood chemistry revealed a highly elevated creatine kinase activity. An orthopedic or vascular etiology of the lameness was excluded by radiographs, computed tomography, and magnetic resonance imaging. Further workup for a neurologic or muscular etiology by electromyography, nerve conduction velocity measurement, and histology of muscle as well as nerve biopsies identified the cause of the lameness. Histology revealed a pyogranulomatous, necrotizing myositis with parasites of the species Trichinella. Furthermore different developmental stages of fungi were detected which were identified as Mucor sp. Treatment with albendazole and itraconazole significantly improved the patient's clinical signs.

Short-term and long-term effects of a minimally invasive transilial vertebral blocking procedure on the lumbosacral morphometry in dogs measured by computed tomography.

OBJECTIVE: To determine the effects of a minimally invasive transilial vertebral (MTV) blocking procedure on the computed tomographic (CT) appearance of the lumbosacral (L7/S1) junction of dogs with degenerative lumbosacral stenosis (DLSS). STUDY DESIGN: Prospective study. ANIMALS: 59 client-owned dogs with DLSS. METHODS: Lumbosacral CT images were acquired with hyperextended pelvic limbs before and after MTV in all dogs. Clinical follow-up was obtained after 1 year, including a neurologic status classified in 4 grades, and if possible, CT. Morphometric measurements (Mean ± SEM) including foraminal area, endplate distance at L7/S1 and LS angle were obtained on sets of reformatted parasagittal and sagittal CT images. RESULTS: The mean foraminal area (ForL) increased from 32.5 ± 1.7 mm2 to 59.7 ± 1.9 mm2 on the left and from 31.1 ± 1.4 mm2 to 59.1 ± 2.0 mm2 on the right (ForR) side after MTV. The mean endplate distance (EDmd) between L7/S1 increased from 3.7 ± 0.1 mm to 6.0 ± 0.1 mm, and mean lumbosacral angle (LSa) from 148.0 ± 1.1° to 170.0 ± 1.1° after MTV. CT measurements were available 1 year postoperatively in 12 cases: ForL: 41.2 ± 3.1 mm2 ; ForR: 37.9 ± 3.1 mm2 ; EDmd: 4.3 ± 0.4 mm, and LSa 157.6 ± 2.1° (values are mean and standard error of mean = SEM). All 39 dogs with long-term follow-up improved by at least 1 neurologic grade, 9/39 improving by 3 grades, 15/39 by 2 grades, and 15/39 by 1 grade. CONCLUSIONS: MTV results in clinical improvement and morphometric enlargement of the foraminal area in dogs with variable degrees of foraminal stenosis. CLINICAL RELEVANCE: MTV may be a valuable minimally invasive option for treatment of dogs with DLSS.

Electroencephalographic recordings in dogs suffering from idiopathic and symptomatic epilepsy: diagnostic value of interictal short time EEG protocols supplemented by two activation techniques.

The diagnostic value of interictal short time electroencephalographic (EEG) recordings in epileptic dogs under general anaesthesia with propofol and the muscle relaxant rocuronium bromide was investigated. Two activation techniques, namely photic stimulation and hyperventilation, were evaluated for their potential to enhance the diagnostic validity of these recordings. Sixty-one dogs suffering from idiopathic epilepsy and 28 dogs suffering from symptomatic epilepsy were included. Electroencephalograms were recorded using five subdermal EEG electrodes (F3, F4, Cz, O1 and O2). All 89 EEGs were analysed visually and 61 were also evaluated quantitatively with fast Fourier transformation. Interictal paroxysmal epileptiform activity was found in 25% of idiopathic and in 29% of symptomatic epileptic dogs. Quantitative analysis of the EEGs (qEEGs) detected significant differences of frequency analysis in single reading points without any continuous changes of frequency bands. A comparison between healthy and affected brain hemispheres in seven dogs with focal lesions of one hemisphere did not show any significant differences in qEEG analysis. qEEG was not more sensitive than visual evaluation. Despite the use of activation techniques, the results showed that short time EEG recordings in epileptic dogs can detect interictal epileptic activity in less than one third of all seizuring dogs and is not a useful screening method.

Evaluation of periodic electrodiagnostic measurements to monitor motor recovery after different peripheral nerve lesions in the rat.

INTRODUCTION: The advantage of minimally invasive electrodiagnostic methods for periodic evaluation of reinnervation at predefined time intervals does not seem to be widely recognized. In this study, using a rat model, we assessed the utility of periodic electrodiagnostic measurements for monitoring ongoing motor recovery after peripheral nerve injuries of differing severity. METHODS: In a comparative study, either unilateral sciatic nerve crush injury (n = 10), end-to-end coaptation (n = 5), or 10-mm nerve autotransplantation (n = 10) were performed. During the 6-16-week period thereafter compound muscle action potentials (CMAPs) were recorded percutaneously every week in anesthetized animals. Motor nerve conduction velocity and percentage of axon loss were calculated and compared with footprint analyses (static sciatic index, SSI) and evaluations of sensory recovery. RESULTS: Our results clearly demonstrate that, although SSI measurements reliably demonstrated progress of regeneration after nerve crush injury only, differences in electrodiagnostically determined values precisely remodeled differences in axonal regeneration, which was confirmed by histomorphometric analysis of axonal regeneration. CONCLUSIONS: Percutaneous electrodiagnostic measurements enable reliable estimation of axonal regeneration parameters such as myelination and nerve fiber density and display in close proximity the actual status of axonal regeneration.

Potassium-aggravated muscle stiffness in 12 cats.

CASE DESCRIPTION: 12 European shorthair cats (6 males and 6 females; age range, 2 months to 3 years) from 1 household were evaluated for clinical signs of recurrent and progressive muscle spasticity. Genetic relationships among the cats were suspected but were not known. CLINICAL FINDINGS: Physical examination of all cats revealed a thin to mildly emaciated body condition and signs of suppurative rhinitis. Results of neurologic evaluations revealed no abnormalities in any cats at rest, but exercise- and stress-induced episodes of muscle spasticity were observed. Results of hematologic (7/12 cats) and CSF (4) analysis, diagnostic imaging (including radiography [7] and magnetic resonance imaging [4]), electromyography (4), motor nerve conduction tests (4), screening for metabolic storage diseases (4), provocation tests via exercise in a cold (4°C [39.2°F]) environment (7), and gross pathological and histologic examination (5) revealed no abnormalities that could potentially explain the clinical signs. However, consumption of a potassium-enriched diet resulted in severe aggravation of clinical signs in 7 of 7 cats, leading to a diagnosis of potassium-aggravated muscle stiffness. TREATMENT AND OUTCOME: 5 cats were euthanized after initial examination because of poor physical condition and severe clinical signs. Spasticity in the 7 remaining cats was improved during a 6-week follow-up period as they reduced their own activity. Further investigation and treatment were declined. CLINICAL RELEVANCE: Channelopathies are rarely recognized diseases in domestic animals. In addition to conventional diagnostic evaluation methods, provocation tests in a clinical environment can be used in the assessment of channelopathies.

Spider silk constructs enhance axonal regeneration and remyelination in long nerve defects in sheep.

BACKGROUND: Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. METHODOLOGY/PRINCIPAL FINDINGS: The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6) was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6) staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery.

Electroencephalographic recordings in dogs: Prevention of muscle artifacts and evaluation of two activation techniques in healthy individuals.

This study was performed to improve a standard anesthetic protocol for electroencephalography (EEG) in dogs and to evaluate the effect of photic stimulation and hyperventilation on the EEG of healthy dogs. Ten clinically and neurologically normal beagle dogs were anesthetized with propofol given intravenously with average doses of 7.5mg/kg for induction and 0.37mg/kg/min constant rate infusion for maintenance. Rocuronium bromide (0.4mg/kg IV) was used as a peripheral muscle relaxant in order to prevent muscle artifacts. EEGs were recorded digitally using five subdermal needle electrodes. Photic stimulation and hyperventilation were performed to evaluate two activation techniques commonly used in human EEG recording methods. Monopolar and bipolar montages were analyzed visually and quantitatively. The use of rocuronium produced muscle artifact-free EEG recordings during the given recording procedure which indicates that rocuronium is a valuable adjunct to anesthesia during EEG recording. Photic stimulation and hyperventilation did not provoke paroxysmal discharges in the EEG of healthy dogs. Analysis of quantitative EEG data showed that background activity did not differ significantly between periods with and without stimulation. This data are important basic values and will further help to compare the effects of photic stimulation and hyperventilation of healthy dogs and those suffering from epilepsy.

[Quantitative study on cultivation of canine myoblasts]. / Quantitative Untersuchungen zur Kultivierung caniner Myoblasten.

Skeletal muscle cell culture is an important tool to discover the pathogenesis of rare canine neuromuscular diseases. The aim of the current study was to improve an existing clinical protocol to extract and cultivate canine myoblasts by using different enzymes for tissue digestion. The contamination of the mixed culture with fibrocytes should be minimized, a higher number of myoblasts with a shorter lag period should be gained and the influence of transport length on the myoblast numbers should be assessed. Twenty-one muscle biopsies (n = 21) from healthy dogs were taken, mechanically trimmed, enzymatically dissociated with either Protease or Trypsin and cultured under identical conditions for 168 hours. To distinguish and quantify myoblasts and fibrocytes an immunocytochemical staining of the muscle cell specific intermediate filament desmin was performed. To analyse the influence of a transport on the samples eight biopsies were cultured with either Trypsin or Protease at the Using Protease a significant higher production and a morphological better proliferation of myoblasts (P = 0.0102) was achieved. The average percentage of myoblasts was 78.96% using Protease and 54.68% using Trypsin. The duration of the transport (1-3 days) did not result in any significant changes in total myoblast cell counts (P = 0.798). This reveals the possibility to send muscle biopsies from distant clinics to a specialised laboratory. In conclusion, the use of Protease is an improvement for cultivating canine myoblasts and provides better conditions for further investigations elucidating pathogenesis of rare neuromuscular diseases.