Effects of high-dose docosahexaenoic acid supplementation as an add-on therapy for canine idiopathic epilepsy: A pilot study.

Background: The anti-epileptic effects of docosahexaenoic acid (DHA) in dogs and humans remain controversial. The dosage and efficacy of DHA were various in the previous reports. Aim: The effects of high-dose DHA supplementation as add-on therapy for idiopathic epilepsy in dogs were evaluated. Methods: An open-label clinical trial was designed in this pilot study. Six dogs (median age: 6 years) with idiopathic epilepsy were included. All the patients were diagnosed with idiopathic epilepsy using magnetic MRI and cerebrospinal fluid examination (median: 2.0 years before the trial). They had 5-45 seizures and/or auras (median: 9.0) in the month before starting DHA supplementation. DHA was adjunctively administered at doses of 69-166 mg/kg/day without changing other prescriptions. Results: Four of the six patients completed the 6-month observation period. All the patients showed a decrease in seizure frequency of 50% or more within 2-3 months after the start of the administration, and three patients decreased to a frequency of 0-1 per month after 5-6 months. No clear adverse events were observed in the general condition or blood test results in any patients. Conclusion: Although the sample size was small and the study was not a randomized controlled trial, the data suggest that add-on supplementation of DHA could be useful in reducing the frequency of seizures in canine idiopathic epilepsy.

Mineral, trace element, and toxic metal concentration in hair from dogs with idiopathic epilepsy compared to healthy controls.

BACKGROUND: Altered trace element status is associated with epilepsy in humans and dogs with idiopathic epilepsy (IE). OBJECTIVES: Compare hair element concentrations in epileptic and healthy dogs. ANIMALS: Sixty-three dogs with IE (53 treated, 10 untreated) and 42 controls. METHODS: Case-control study using ICP-MS to determine hair calcium, magnesium, phosphorus, sodium, potassium, iron, copper, manganese, zinc, selenium, chromium, lead, mercury, cadmium, arsenic, aluminum, and nickel concentration. Groups were compared using nonparametric tests. Results were controlled for diet, sex, age, and hair color using generalized linear mixed models. RESULTS: Compared to healthy controls, dogs with IE had lower hair phosphorus (mean ± SD; IE: 286.19 ± 69.62 µg/g, healthy: 324.52 ± 58.69 µg/g; P = .001), higher hair copper (IE: 10.97 ± 3.51 µg/g, healthy: 8.41 ± 1.27 µg/g; P < .001), zinc (IE: 158.25 ± 19.64 µg/g, healthy: 144.76 ± 32.18 µg/g; P < .001), copper/zinc ratio (IE: 0.07 ± 0.02, healthy: 0.06 ± 0.01; P = .003), selenium (IE: 1.65 ± 0.43 µg/g, healthy: 0.94 ± 0.73 µg/g; P < .001), and arsenic (IE: 0.40 ± 0.78 µg/g, healthy: 0.05 ± 0.08 µg/g; P < .001). When comparing treated and untreated epileptic dogs with healthy dogs, the differences in phosphorus and selenium remained significant for both groups, whereas the differences in copper, zinc, and arsenic were significant only for treated dogs. Potassium bromide treatment was strongly associated with high hair arsenic (P = .000). CONCLUSIONS AND CLINICAL IMPORTANCE: Altered trace element status could be involved in the pathophysiology of IE in dogs. Antiseizure drugs might affect trace element and arsenic metabolism.

Neurosurgery in feline epilepsy, including clinicopathology of feline epilepsy syndromes.

Feline epilepsy is treated with antiseizure medications, which achieves fair to good seizure control. However, a small subset of feline patients with drug-resistant epilepsy requires alternative therapies. Furthermore, approximately 50 % of cats with epileptic seizures are diagnosed with structural epilepsy with or without hippocampal abnormality and may respond to surgical intervention. The presence of hippocampal pathology and intracranial tumors is a key point to consider for surgical treatment. This review describes feline epilepsy syndrome and epilepsy-related pathology, and discusses the indications for and availability of neurosurgery, including lesionectomy, temporal lobectomy with hippocampectomy, and corpus callosotomy, for cats with different epilepsy types.

Use of cannabis in the treatment of animals: a systematic review of randomized clinical trials.

Cannabis is used in the treatment of several human conditions; however, its use is still less explored in veterinary medicine. This systematic review aims to summarize the evidence of efficacy and safety of the use of cannabis for the treatment of animal disease. A literature search was performed for studies published until 16 March 2021 in five databases. Randomized clinical trials (RCTs) that reported the efficacy or safety of cannabis in the treatment of animal disease were included. The RoB 2 Tool was used to assess the risk of bias. A total of 2427 records were identified, of which six studies fully met the eligibility criteria. RCTs were conducted in dogs with osteoarthritis (n = 4), with epilepsy (n = 1), and with behavioral disorders (n = 1). All studies used cannabidiol (CBD) oil in monotherapy or in combination with other drugs. Studies used CBD at 2 or 2.5 mg kg-1 twice daily (n = 4), orally (n = 5), during 4 or 6 weeks (n = 3), and compared CBD with placebo (n = 5). CBD significantly reduced pain and increased activity in dogs with osteoarthritis (n = 3). Moreover, CBD significantly reduced the frequency of seizures in dogs with epilepsy (n = 1) and the aggressive behavior of dogs (n = 1). Although promising results were identified, studies were heterogeneous and presented risks of bias that required caution in the interpretation of findings. Therefore, there was some evidence to support the use of CBD in dogs with osteoarthritis to reduce pain and increased activity, but limited evidence against epilepsy and behavioral problems. In addition, CBD was well tolerated with mild adverse effects. More RCTs with high quality of evidence are needed, including greater numbers of animal subjects, additional species, and clear readout measures to confirm these findings.

A multicenter randomized controlled trial of medium-chain triglyceride dietary supplementation on epilepsy in dogs.

BACKGROUND: Medium-chain triglyceride (MCT) enriched diet has a positive effect on seizure control and behavior in some dogs with idiopathic epilepsy (IE). OBJECTIVE: To evaluate the short-term efficacy of MCTs administered as an add-on dietary supplement (DS) to a variable base diet to assess seizure control and antiseizure drug's (ASD) adverse effect profiles. ANIMALS: Twenty-eight dogs with International Veterinary Epilepsy Task Force Tier II (IVETF) level diagnosis of treated IE with 3 or more seizures in the last 3 months were used. METHODS: A 6-month multicenter, prospective, randomized, double-blinded, placebo-controlled crossover trial was completed, comparing an MCT-DS with a control-DS. A 9% metabolic energy-based amount of MCT or control oil was supplemented to the dogs' diet for 3 months, followed by a control oil or MCT for another 3 months, respectively. Dogs enrolled in this study satisfied most requirements of IE diagnosis stated by the IVETF II level. If they received an oil DS or drugs that could influence the metabolism of the investigated DS or chronic ASD, the chronic ASD medication was adjusted, or other causes of epilepsy were found, the dogs were excluded from the study. RESULTS: Seizure frequency (median 2.51/month [0-6.67] versus 2.67/month [0-10.45]; P = .02) and seizure-day frequency were significantly (1.68/month [0-5.60] versus 1.99/month [0-7.42], P = .01) lower when dogs were fed MCT-DS in comparison with the control-DS. Two dogs were free of seizures, 3 had ≥50% and 12 had <50% reductions in seizure frequency, and 11 dogs showed no change or an increase in seizure frequency. CONCLUSIONS AND CLINICAL IMPORTANCE: These data show antiseizure properties of an MCT-DS compared to a control oil and support former evidence for the efficacy of MCTs as a nutritive, management option for a subpopulation of drug-resistant dogs with epilepsy.

A double-blinded randomised dietary supplement crossover trial design to investigate the short-term influence of medium chain fatty acid (MCT) supplement on canine idiopathic epilepsy: study protocol.

BACKGROUND: Epilepsy is the most common brain disease in dogs. Recently, diets have been reported to have a positive impact on seizure activity and behaviour in various species including dogs with idiopathic epilepsy (IE). Historically, classic high fat ketogenic diets (KD) and medium chain triglycerides (MCT) KD have been successfully used to manage drug-resistant epilepsy. Similarly, an MCT enriched diet has been shown to improve seizure control and behavioural comorbidities in some dogs with IE. However, it is unknown whether an MCT dietary supplement (DS) may provide similar positive effects. METHODS: A 6-month prospective, randomised, double-blinded, placebo-controlled, crossover, multicentre dietary trial is designed comparing a 9% metabolic energy based calculated medium-chain triglyceride (MCT) oil supplement to a conventional 'control' DS. Only dogs which will have an International Veterinary Epilepsy Task Force Tier II level like diagnosis of IE which satisfied the following inclusion criteria are included: age between 6 months and ≤ 12 years; weighing between 4 and ≤ 65 kg; unremarkable interictal neurological examinations; no clinically significant findings on routine laboratory diagnostics; unremarkable brain MRI scan; have had at least 3 seizures in the previous 3 months prior to enrolment; treated with at least one ASD and being classified as resistant. All dogs are fed initially for 90 ± 2 days with either the control oil or the MCT oil alongside their normal diet, followed by 97 ± 2 days with the other supplement including a 7-day washout period. Overall, the aim is to recruit thirty-six patients at five different centres and to investigate the effect of MCTs as DS on seizure activity, tolerability, behavioural comorbidities and quality of life (QoL). DISCUSSION: Dietary interventions are rarely studied in a standardised form in veterinary medicine. The background diet, the cohort of animals and ASD received is standardised in this prospective diet trial to ensure representative data about the potential effect of MCT DS. If the study data confirms former findings, this would provide further evidence for the efficacy of MCTs as a management option for canine epilepsy. This publication should offer a repository of trial conditions and variable description with forecasted statistical analysis.

Investigating owner use of dietary supplements in dogs with idiopathic epilepsy.

Epilepsy is the most common chronic neurological disorder in dogs. Some diets have been shown to have a positive impact upon the seizure activity in dogs with idiopathic epilepsy (IE), while other diets and dietary supplements (DS), although marketed as providing health benefits, lack conclusive scientific evidence on their actual beneficial effects. A web-based owner questionnaire was designed to assess how and why owners of dogs with IE use different dietary regimes and DS. The study cohort, with 297 valid responses, consisted mainly of pure-breed (82.5%) male neutered (52.9%) dogs. Over two-thirds of owners (67.7%) changed their dog's diet after their dog received a diagnosis of IE. Nearly half of the owners (45.8%) reported giving DS, the most common being coconut oil or derived medium-chain triglyceride oil (71.3%). Some owner justifications of DS use included improvement of seizure frequency (88.2%), seizure severity (61.8%) and protection from potential drug side effects (62.5%). Many owners give DS to their dog with IE. The pharmacokinetic properties of anti-epileptic drugs, such as efficacy, absorption and clearance can be influenced by other medications, diets and possibly by DS. We propose that use of DS should be considered and monitored by veterinary surgeons in epilepsy management.

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs.

This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision-making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine.

Effects of essential fatty acid supplementation in dogs with idiopathic epilepsy: a clinical trial.

The effects of essential fatty acid supplementation (EFA) on the control of idiopathic epilepsy in dogs were investigated in a blinded, placebo-controlled trial. Fifteen dogs were treated with triple purified Ω-3 oil containing 400 mg eicosapentaenoic acid, 250 mg docosahexaenoic acid and 22 mg vitamin E per 1.5 mL at a dose of 1.5 mL/10 kg once daily for 12 weeks, followed by a 12 week placebo period of supplementation with olive oil. Owners recorded seizure frequency and severity and any adverse events. EFA supplementation did not reduce seizure frequency or severity in dogs with idiopathic epilepsy.

Tratamento homeopático de epilepsia canina: relato de caso / Homeopathic treatment of canine epilepsy: a case report

A epilepsia é a doença neurológica crônica mais comum em cães caracterizada pela manifestação de crises convulsivas recorrentes e involuntárias, com ou sem perda de consciência; a epilepsia de etiologia idiopática é a mais frequente nessa espécie. No caso relatado a cadela Mel, que recebeu o diagnóstico de epilepsia idiopática, foi submetida ao tratamento homeopático, sem associação com medicamentos alopáticos, cuja prescrição inclui os medicamentos homeopáticos Pulsatilla nigricans e Cicuta virosa, em diferentes potências e frequências ao longo da evolução clínica do paciente. A resposta terapêutica foi muito satisfatória, promovendo controle eficaz das convulsões com qualidade de vida do animal e seu proprietário, atingindo com sucesso os objetivos do tratamento sem expor o paciente a qualquer tipo de risco. Portanto, a homeopatia demonstrou ser uma opção terapêutica segura e eficiente para a epilepsia canina.

Positive impact of omega-3 fatty acid supplementation in a dog with drug-resistant epilepsy: a case study.

Epilepsy is the most common neurological disorder in both dogs and humans. Although the pharmacological options for treatment of epilepsies have increased, it has been reported that two-thirds of dogs with epilepsy are refractory to antiepileptic drug therapy. To our knowledge, there are no experimental studies in the literature that show an effect of omega-3 supplementation on epilepsy in dogs. Our case study describes the effectiveness of daily intake of a moderate amount of fish oil in a case of canine epilepsy.

Clinical management of idiopathic epilepsy in dogs with homeopathic Belladonna 200C: a case series.

Epilepsy is an important neurological disorder in dogs. Belladonna 200C was evaluated in 10 dogs with idiopathic epilepsy. During the seizure phase, 3-4 drops of Belladonna 200C were administered orally at 15 min intervals until considerable reduction in seizure activity, then four times daily. Four dogs with head shaking syndrome in addition to seizures were given Cocculus 6C, 3-4 drops orally weekly for 3 months in addition. Numbers of fits reduced to 2-3 during first 2 weeks post-therapy and then became occasional in next 2 weeks. With continuation of Belladonna therapy, no fits were observed during 2-7 months follow-up. In two cases epileptic fits reappeared within 15-25 days of cessation of therapy. Belladonna therapy was resumed and seizure control was again achieved. Owners were advised to continue the therapy at least twice daily until there were no fits for 2-3 months. Liver specific enzymes were monitored, no abnormalities were observed.

Anticonvulsant activity and tolerance of ELB138 in dogs with epilepsy: a clinical pilot study.

A new antiepileptic and anxiolytic drug, ELB138, was evaluated in a clinical pilot study in dogs with newly diagnosed or chronic idiopathic epilepsy. The purpose was to verify clinically the anticonvulsant effectiveness of this substance, which had already been demonstrated experimentally. Data from 29 dogs treated with ELB138 were compared with results obtained retrospectively from 82 dogs treated with conventional antiepileptic medication. The reduction in seizure frequency using ELB138 in dogs with newly diagnosed idiopathic epilepsy was comparable to the reduction in dogs treated either with phenobarbital or primidone. In dogs with chronic epilepsy and add-on therapy with either ELB138 or potassium bromide, such supplementation reduced the seizure frequency and the duration and severity of seizures. The most obvious difference between ELB138 treatment and conventional medications became clear in the evaluation of side effects, which in those dogs treated with ELB138 were rare, and consisted mostly of transient polyphagia. This pilot study confirmed that ELB138 has a potent anticonvulsant effect in dogs with idiopathic epilepsy. These results will form the basis for a multicentre, blinded study.

Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent.

OBJECTIVE: To assess whether there is a change in seizure activity in dogs with refractory epilepsy that are receiving appropriate doses of phenobarbitone and/or potassium bromide, when gabapentin is added to the therapeutic regimen. DESIGN: A prospective study of 17 dogs with a refractory seizure disorder, 16 of which have idiopathic epilepsy. PROCEDURE: Patients were stabilised using phenobarbitone and/or potassium bromide to produce tolerable therapeutic serum concentrations and dosed additionally with gabapentin at 35 to 50 mg/kg/d (divided twice or three times daily) for 4 months. Owners recorded seizure activity and side effects during this period in a standardised diary. Patients underwent monthly physical examinations and venepuncture to assess selected serum biochemical analytes, as well as phenobarbitone and bromide concentrations. Patients were further monitored for long-term response to adjunctive gabapentin therapy. RESULTS: There was no significant decrease in the number of seizures over the study period for the entire cohort, however three dogs stopped seizuring completely. There was a significant increase in the number of patients who showed an increase in the interictal period (P > 0.001). Serum alkaline phosphatase activity and triglyceride concentrations were elevated at baseline. There were no significant changes in biochemical analytes during the course of the study period. Side effects observed initially on addition of gabapentin included sedation and hind limb ataxia. The former resolved spontaneously after a few days; the latter after a slight reduction in bromide dose. Long-term, a further two patients became seizure free and ten patients remained on gabapentin indefinitely. No long-term side effects have become apparent. CONCLUSION: Addition of gabapentin to phenobarbitone and/or potassium bromide increased the interictal period and shortened the post-seizure recovery in some canine epileptics. In some dogs, seizures were prevented completely, while in others there was an increase in interictal period. The short-half life of gabapentin has advantages for seizure control, however its present high cost may prohibit therapy in large dogs.

Use of vagal nerve stimulation as a treatment for refractory epilepsy in dogs.

OBJECTIVE: To evaluate safety and efficacy of vagal nerve stimulation in dogs with refractory epilepsy. DESIGN: Placebo-controlled, double-masked, crossover study. ANIMALS: 10 dogs with poorly controlled seizures. PROCEDURE: A programmable pacemaker-like device designed to deliver intermittent stimulation to the left cervical trunk of the vagus was surgically implanted in each dog. Dogs were assigned randomly to two 13-week test periods, 1 with nerve stimulation and 1 without nerve stimulation. Owners recorded data on seizure frequency, duration, and intensity, as well as adverse effects. RESULTS: No significant difference in seizure frequency, duration, or severity was detected between overall 13-week treatment and control periods. During the final 4 weeks of the treatment period, a significant decrease in mean seizure frequency (34.4%) was detected, compared with the control period. Complications included transient bradycardia, asystole, and apnea during intraoperative device testing, and seroma formation, subcutaneous migration of the generator, and transient Horner's syndrome during the 14-day period between surgery and suture removal. No adverse effects of stimulation were detected, and most owners were satisfied with the treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Vagal nerve stimulation is a potentially safe approach to seizure control that appears to be efficacious in certain dogs and should be considered a possible treatment option when antiepileptic medications are ineffective.

Nimodipine for treatment of idiopathic epilepsy in dogs.

OBJECTIVE: To evaluate efficacy and safety of the calcium channel antagonist nimodipine in dogs with idiopathic epilepsy. DESIGN: Prospective clinical trial. ANIMALS: 10 dogs with idiopathic epilepsy. Dogs were included if seizures were inadequately controlled despite treatment with barbiturates and serum phenobarbital concentrations were > 25 micrograms/ml, if dogs had intolerable adverse effects when treated with barbiturates, or if dogs had mild, inadequately treated seizures. PROCEDURES: Dogs were treated with nimodipine (2.5 mg/kg [1.1 mg/lb] of body weight, PO, q 12 h), and other medications were slowly withdrawn. Dogs were monitored for seizure frequency and severity as well as any adverse effects to the medication. RESULTS: Few adverse effects were reported. Seizure control, however, was generally inadequate. All but 2 dogs were withdrawn from the study because of poor seizure control. Plasma nimodipine concentrations were low, with a mean peak concentration of 105.3 ng/ml. CLINICAL IMPLICATIONS: Nimodipine was not successful in controlling seizures in dogs used in this study.

An auricular acupuncture treatment for idiopathic canine epilepsy: a preliminary report.

A new canine auricular acupuncture point for the treatment for epilepsy is introduced. The new acupoint was used with a previously reported canine auricular acupoint (van Neikerk and Eckersley, 1988) for the treatment of epilepsy in five dogs. The testimonial results of these five cases indicate that the technique is worthy of scientific investigation, and controlled research is proposed. Only testimonial evidence currently supports its application, yet this innocuous treatment is recommended for use in all cases of canine epilepsy. The traditional Chinese medical explanation for the treatment is described, and hypothetical Western physiology is presented.