Refractory Idiopathic Epilepsy Research Articles

Telmisartan as an add-on treatment for dogs with refractory idiopathic epilepsy: a nonrandomized, uncontrolled, open-label clinical trial.

To evaluate the effect on seizure frequency of add-on telmisartan treatment in dogs with refractory idiopathic epilepsy. 11 client-owned dogs with idiopathic epilepsy and ≥ 2 generalized seizures/mon that were currently being treated with ≥ 2 antiepileptic drugs. Telmisartan was administered at a dosage of 0.25 to 1 mg/kg, PO, every 12 hours for 4 to 16 months. Seizure frequencies before and during telmisartan treatment were recorded. 10 dogs completed the 4-month treatment protocol. One dog was excluded owing to a transient increase in serum creatinine concentration; no adverse effects of telmisartan were observed in the remaining 10 dogs. A reduction in seizure frequency greater than an estimated expected placebo effect of 30% was evident in 7 of the 10 dogs. Long-term (12 to 16 months) follow-up information was available for 6 dogs, of which 4 had a further reduction in seizure frequency. Differences in seizure frequency were not statistically significant. No significant difference was found in serum phenobarbital concentration throughout the treatment period in the 7 dogs that were tested. Telmisartan has the potential to reduce seizure frequency when administered as an add-on antiepileptic drug in dogs with refractory idiopathic epilepsy. A randomized, double-blind, placebo-controlled trial is needed to determine the true efficacy of telmisartan. On the basis of our results, a sample size of 54 dogs with refractory idiopathic epilepsy would be needed.

Evaluation of the Chinese Herbal Formula Di Tan Tang as an Oral Add-On Therapy for Dogs with Presumptive Refractory Idiopathic Epilepsy: An Open-Label Investigation in 8 Dogs

Idiopathic (genetic) epilepsy is a common neurologic disorder of dogs and 25%-30% of these dogs are refractory to antiseizure drug therapy. The purpose of this open-label clinical trial was to evaluate the potential efficacy and tolerability of a traditional Chinese herbal formula Di Tan Tang as an add-on therapy for dogs with refractory presumptive idiopathic epilepsy. Eight dogs with refractory presumptive idiopathic epilepsy were evaluated for seizure frequency 3 months prior to and 3 months after instituting oral Di Tan Tang therapy (0.5g/10lbs body weight, q 12 hrs) using a prospective open-label, non-comparative clinical trial design. The overall mean reduction in seizure frequency after treatment with Di Tan Tang for the 8 dogs was significant (p=0.035) at 27%, with 2 dogs qualifying as responders (≥50% reduction in seizure frequency). One dog experienced mild sedation after starting Di Tan Tang; no other adverse effects were recorded for the remaining dogs. The results of this preliminary investigation suggest that Di Tan Tang may be a useful adjunctive treatment option for dogs with refractory epilepsy. Further clinical investigation into the potential use of Di Tan Tang in canine refractory epilepsy is warranted.

ABCB1 c.-6-180T > G polymorphism and clinical risk factors in a multi-breed cohort of dogs with refractory idiopathic epilepsy

Epilepsy is the most common chronic neurological disorder in dogs. Approximately 20–30% of dogs do not achieve satisfactory seizure control with two or more anti-epileptic drugs at appropriate dosages. This condition, defined as refractory epilepsy, is a multifactorial condition involving both acquired and genetic factors. The P glycoprotein might play and important role in the pathophysiological mechanism and it is encoded by the ABCB1 gene. An association between a single nucleotide variation of the ABCB1 gene (c.-6-180T>G) and phenobarbital resistance has previously been reported in a Border collie population with idiopathic epilepsy. To date, the presence and relevance of this polymorphism has not been assessed in other breeds. A multicentre retrospective, case-control study was conducted to investigate associations between ABCB1 c.-6-180T>G, clinical variables, and refractoriness in a multi-breed population of dogs with refractory idiopathic epilepsy. A secondary aim was to evaluate the possible involvement of the ABCB1 c.-6-180T>G single nucleotide variation this population.Fifty-two refractory and 50 responsive dogs with idiopathic epilepsy were enrolled. Of these, 45 refractory and 50 responsive (control) dogs were genotyped. The G allele was found in several breeds, but there was no evidence of association with refractoriness (P=0.69). The uncertain role of the c.-6-180T>G variation was further suggested by an association between the T/T genotype with both refractoriness and responsiveness in different breeds. Furthermore, high seizure density (cluster seizure) was the main clinical risk factor for refractory idiopathic epilepsy (P=0.003).

Should Levetiracetam or Imepitoin Be Used in Preference as Second-line Treatment in Pharmacoresistent Epileptic Cats?

PICO questionIn adult cats with idiopathic epilepsy, which is poorly controlled with phenobarbital monotherapy, should levetiracetam or imepitoin be used in preference as a second line treatment in order to reduce seizure frequency?Clinical bottom lineThere is currently insufficient evidence to reliably determine whether levetiracetam or imepitoin should be used in preference as a second line treatment for the management of cats with refractory idiopathic epilepsy. There is weak evidence however to suggest clinical efficacy of levetiracetam and imepitoin in management of cats with idiopathic epilepsy. Further studies which evaluate and directly compare the efficacy of second line anticonvulsants in feline epilepsy are needed.

Hypoallergenic diet may control refractory epilepsy in allergic children: A quasi experimental study

Recent data has suggested a definitive role for inflammatory processes in the pathophysiology of epilepsy. In this study we hypothesized that food allergies, as chronic inflammatory processes, underlie the pathophysiology of refractory idiopathic epilepsy and investigated whether food elimination diets may assist in managing refractory epilepsy. The study was conducted on 34 patients up to 16 years of age with refractory convulsions who attended the Allergy Outpatient Clinic, Mofid Children Hospital between 2015 and 2016 with youngest and oldest participants at ages of 3 months and 16 years old, respectively. The participants were categorized into three groups according to the results of skin prick test and serum specific IgE measurements. Elimination diets were instituted for the patients with non IgE-mediated and mixed food allergies. The study was conducted for a period of 12 weeks. The participants were assessed for at least 50% reduction in number of seizures following the intervention. There was a significant reduction in number of seizures (p < 0.001) following the intervention. Seventeen patients (50%) did not experience any seizures after 8 weeks of treatment and 12 patients (35%) had a significant (51–99%) decrease in the number of their seizures. Five patients did not show any changes in their daily seizure frequency. The obtained data suggest that food allergy may play a role in triggering refractory epilepsies and their adequate response to treatment. A trial of elimination diet showed more than 50% seizure reduction in more than 85% of the children studied. However, we believe these results are preliminary and they motivate a fully controlled study in the future.

Topiramate as an add‐on antiepileptic drug in treating refractory canine idiopathic epilepsy

To evaluate the efficacy and safety of topiramate as an add-on therapy in dogs with refractory idiopathic epilepsy. Prospective, open label, non-comparative clinical trial of topiramate in dogs with idiopathic epilepsy and poor seizure control despite therapeutic serum concentrations of phenobarbital and potassium bromide. The efficacy of topiramate was evaluated by comparing seizure and seizure day frequencies during a retrospective 2-month period with a prospective short-term follow-up of 6 months. An additional long-term follow-up period ranging from 3 to 9 months was conducted on dogs that responded to topiramate therapy during the short-term follow-up. Ten dogs were included. Five (50%) responded to topiramate therapy during the short-term follow-up showing a significant (P=0·04) decrease of 66% in seizure frequency. Three of the five dogs remained responders during the long-term follow-up. Weight loss, sedation and ataxia were the most common adverse effects of topiramate therapy, but in dogs with moderate sedation or ataxia, signs subsided in a few weeks to few months to mild sedation or ataxia. Topiramate may be effective as an add-on medication in treating canine idiopathic epilepsy. Apart from sedation and ataxia reported in some of the dogs, topiramate was well-tolerated.

Relationship between Celiac Disease and Refractory Idiopathic Epilepsy in Children

Objective Epilepsy occurs with a yearly incidence of 40 per 100,000 children, of which more than 25% are resistant to drug therapy. Epilepsy may occur in autoimmune diseases like lupus, celiac disease and myasthenia gravis. In this study, the relationship between celiac disease and refractory epilepsy was evaluated in children with idiopathic epilepsy. Material & Methods Hundred-fifty-five children (mean age, 6.7±3.3 years) with idiopathic and cryptogenic epilepsy referred to the neurology clinic were studied in two groups; drug controlled epilepsy (control, 82 patients) and refractory epilepsy groups (case, 73 patients). Both groups underwent serological tissue transglutaminase antibody measurement by ELISA. In seropositive cases, small intestine biopsy was conducted. Data analysis was performed using student's t test and 2 test. Results Seven (0.04%) patients had celiac disease based on a positive tissue transglutaminase antibody and three patients (0.01%) based on a positive biopsy. Three patients (2.4%) with drug controlled epilepsy (control group) and five with refractory epilepsy (case group) had seropositive celiac disease (p=0.255). In the biopsy survey of six seropositive patients, one patient (1.2%) in the drug controlled epilepsy and two patients (2.7%) in the refractory epilepsy group had positive biopsy for celiac disease (p = 0.604). One seropositive patient did not cooperate for biopsy. Conclusion If the relationship between celiac disease and epilepsy, especially in cases of symptomatic or oligosymptomatic celiac is proved, using gluten free diet increases the ability to control epilepsy particularly in refractory cases. We suggest celiac disease survey is not required in patients with idiopathic epilepsy.

Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs

Investigation of the efficacy of zonisamide as an add-on therapy in dogs with refractory epilepsy. Thirteen dogs fulfilled the inclusion criteria of poor seizure control despite adequate serum levels of phenobarbital, potassium bromide or both. One further dog was treated with zonisamide as monotherapy because of severe blood dyscrasia due to phenobarbital treatment. Various seizure parameters were evaluated retrospectively for a four month period without zonisamide and prospectively for the same time period under zonisamide add-on therapy. The study time period was extended by up to 17 months to evaluate long-term outcome. Data of 11 dogs could be evaluated: nine of them were responders. The median reduction of seizure frequency of all dogs on zonisamide add-on therapy was 70 per cent (range 14 to 100 per cent). Only transient central nervous system side effects were reported. No further increase of liver enzymes occurred. In three of the responder dogs, seizure control subsided after individual time periods (between 69 days and seven months). In dogs with refractory epilepsy, zonisamide may have a beneficial effect on seizure control. In three responder dogs, seizure activity relapsed possibly because of an induction of tolerance. Limiting factors are the high costs.

Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy

Eleven dogs diagnosed with refractory idiopathic epilepsy were treated orally with gabapentin for a minimum of three months at an initial dose of 10 mg/kg every eight hours. They were...