Treatment Of Canine Epilepsy Research Articles

Survey of electroencephalography usage and techniques for dogs.

Canine epilepsy is a chronic common neurologic condition where seizures may be underreported. Electroencephalography (EEG) is the patient-side test providing an objective diagnostic criterion for seizures and epilepsy. Despite this, EEG is thought to be rarely used in veterinary neurology. This survey study aims to better understand the current canine EEG usage and techniques and barriers in veterinary neurology. The online Qualtrics link was distributed via listserv to members of the American College of Veterinary Internal Medicine (ACVIM) Neurology Specialty and the European College of Veterinary Neurology (ECVN), reaching at least 517 veterinary neurology specialists and trainees worldwide. The survey received a 35% response rate, for a total of 180 participant responses. Fewer than 50% of veterinary neurologists are currently performing EEG and it is performed infrequently. The most common indication was to determine a discrete event diagnosis. Other reasons included monitoring treatment, determining brain death, identifying the type of seizure or epilepsy, localizing foci, sleep disorders, for research purposes, and post-op brain surgery monitorization. Most respondents interpreted their own EEGs. Clinical barriers to the performance of EEG in dogs were mainly equipment availability, insufficient cases, and financial costs to clients. This survey provides an update on EEG usage and techniques for dogs, identifying commonalities of technique and areas for development as a potential basis for harmonization of canine EEG techniques. A validated and standardized canine EEG protocol is hoped to improve the diagnosis and treatment of canine epilepsy.

Tratamento da epilepsia em cães – revisão

Epilepsy is relatively common in dogs and is characterized by recurring seizures. In order to treat such cases effectively, the veterinarian must first clarify the etiology of the reported episodic events, investigate the cause of the seizures, carry out a detailed clinical evaluation of the patient from the start of the treatment, decide on the drug to be used, monitor the patient appropriately, and ensure that the dog’s owners understand and collaborate with the treatment. Reasons for treatment failures include the prescription of drugs unsuitable for use in dogs or the use of low doses. This article reviews factors related to the use of phenobarbital, potassium bromide and levetiracetam – drugs available in Brazil for which there is stronger evidence of safety and effectiveness in the treatment of canine epilepsy.

A single-blinded phenobarbital-controlled trial of levetiracetam as mono-therapy in dogs with newly diagnosed epilepsy

Treatment of canine epilepsy is problematic. Few antiepileptic drugs have proven efficacy in dogs and undesirable adverse effects and pharmacoresistance are not uncommon. Consequently, the need for investigation of alternative treatment options is ongoing. The objective of this study was to investigate the efficacy and tolerability of levetiracetam as mono-therapy in dogs with idiopathic epilepsy. The study used a prospective single-blinded parallel group design. Twelve client-owned dogs were included and were randomised to treatment with levetiracetam (30 mg/kg/day or 60 mg/kg/day divided into three daily dosages) or phenobarbital (4 mg/kg/day divided twice daily). Control visits were at days 30, 60 and then every 3 months for up to 1 year. Two or more seizures within 3 months led to an increase in drug dosage (levetiracetam: 10 mg/kg/day, phenobarbital: 1 mg/kg/day). Five of six levetiracetam treated dogs and one of six phenobarbital treated dogs withdrew from the study within 2–5 months due to insufficient seizure control.In the levetiracetam treated dogs there was no significant difference in the monthly number of seizures before and after treatment, whereas in the phenobarbital treated dogs there were significantly (P = 0.013) fewer seizures after treatment. Five phenobarbital treated dogs were classified as true responders (≥50% reduction in seizures/month) whereas none of the levetiracetam treated dogs fulfilled this criterion. Adverse effects were reported in both groups but were more frequent in the phenobarbital group. In this study levetiracetam was well tolerated but was not effective at the given doses as mono-therapy in dogs with idiopathic epilepsy.

Characteristics of selected second-generation antiepileptic drugs used in dogs

A significant number of cases of clinical canine epilepsy remain difficult to control in spite of the applied treatment. At the same time, the range of antiepileptic drugs is increasingly wide, which allows efficient treatment. In the present paper we describe the pharmacodynamics and pharmacokinetics of the newer antiepileptic drugs which were licensed after 1990 but are still not widely used in veterinary medicine. The pharmacokinetic profiles of six of these drugs were tested on dogs. The results of experimental studies suggest that second generation antiepileptic drugs may be applied in mono- as well as in poli- treatment of canine epilepsy because of the larger safety margin and more advantageous pharmacokinetic parameters. Knowledge of the drugs' pharmacokinetics allows its proper clinical appliance, which, in turn, gives the chance to improve the efficiency of pharmacotherapy of canine epilepsy.

Pharmacokinetics of oral rufinamide in dogs

The objective of this study was to determine the pharmacokinetic properties and short-term adverse effect profile of single-dose oral rufinamide in healthy dogs. Six healthy adult dogs were included in the study. The pharmacokinetics of rufinamide were calculated following administration of a single mean oral dose of 20.0 mg/kg (range 18.6-20.8 mg/kg). Plasma rufinamide concentrations were determined using high-performance liquid chromatography, and pharmacokinetic data were analyzed using commercial software. No adverse effects were observed. The mean terminal half-life was 9.86 ± 4.77 h. The mean maximum plasma concentration was 19.6 ± 5.8 μg/mL, and the mean time to maximum plasma concentration was 9.33 ± 4.68 h. Mean clearance was 1.45 ± 0.70 L/h. The area under the curve (to infinity) was 411 ± 176 μg · h/mL. Results of this study suggest that rufinamide given orally at 20 mg/kg every 12 h in healthy dogs should result in a plasma concentration and half-life sufficient to achieve the therapeutic level extrapolated from humans without short-term adverse effects. Further investigation into the efficacy and long-term safety of rufinamide in the treatment of canine epilepsy is warranted.

High‐performance liquid chromatographic analysis of lacosamide in canine serum using ultraviolet detection: application to pre‐clinical pharmacokinetics in dogs

A method for analysis of lacosamide [(R)-2-acetamido-N-benzyl-3-methoxypropionamide] is needed for both human and veterinary pharmacokinetic investigations. While lacosamide is currently used to manage partial-onset seizures in humans suffering from epilepsy, it is also presently being investigated for use in the treatment of canine epilepsy in veterinary medicine. Currently, no dosing regimen for the drug exists in dogs. A novel and simple high-performance liquid chromatography method was developed for determination of lacosamide in dog serum. Serum proteins (0.1 mL) were precipitated with -20.0°C acetonitrile after addition of the internal standard, daidzein. Separation was achieved with a Phenomenex® Luna® C₁₈ (2) (5 µm, 250 × 4.60 mm) column with ultraviolet detection at 210 nm. The calibration curves were linear ranging from 0.5 to 25 µg/mL. Precision of the assay was <13% (RSD) and was within 12% for all points in the calibration curve. The limit of quantitation for this method was 0.5 µg/mL. The assay was applied successfully to a pre-clinical study of lacosamide pharmacokinetics in dogs.

Canine epilepsy: What can we learn from human seizure disorders?

Epilepsy is a common neurological disorder in both dogs and humans. It is refractory to therapy in approximately one-third of canine patients, and even with the advent of new antiepileptic drugs for humans, appropriate treatment options in dogs remain limited. The pathogenesis and pathophysiology of epilepsy is being studied extensively in both human patients and rodent models of experimental epilepsy at the cellular and molecular level, but very little is known about the aetiologies of epilepsies in dogs. In this review, canine epilepsy will be discussed with reference to the human epilepsies and experimental epilepsy research. There is much work to be done in order to classify canine seizure types and breed-specific epileptic syndromes, particularly with reference to electroencephalographic abnormalities and possible genetic abnormalities. The review considers the appropriate use of antiepileptic drugs: phenobarbitone and potassium bromide are effective in most canine patients, although dosing regimes need to be carefully tailored to the individual, with serum concentration measurement. However, a significant proportion of patients remains refractory to these drugs. Work is currently underway to test the efficacy of newer antiepileptic drugs in the treatment of canine epilepsy, and preliminary data suggest that human drugs such as levetiracetam and gabapentin are of benefit in dogs with refractory epilepsy.

Plasma levels of valproic acid and its metabolites during continued treatment in dogs.

Dogs were treated with the anti-epileptic drug valproic acid (VPA) for 2 weeks in order to determine whether therapeutic plasma levels could be maintained. VPA (as the sodium salt) was administered in a dosage of 170-180 mg/kg/day divided into three equal doses in the form of enteric-coated tablets. Due to the rapid elimination of this drug in dogs, therapeutic plasma levels were reached only intermittently. However, the concentrations maintained may be sufficient for anti-epileptic therapy in dogs because the lower plasma protein binding of VPA in this species gives rise to higher central concentrations compared with man. Furthermore, some VPA metabolites previously shown to exert anticonvulsant activity (2-en-VPA and 3-keto-VPA) were found in relatively high concentrations in dog plasma. We would recommend the dosages used in this study as a basis for assessment of VPA in the treatment of canine epilepsy.