Treatment Of Idiopathic Epilepsy Research Articles

Safety and efficacy of cannabidiol-cannabidiolic acid rich hemp extract in the treatment of refractory epileptic seizures in dogs.

The use of cannabidiol (CBD) in childhood refractory seizures has become a common therapeutic approach for specific seizure disorders in human medicine. Similarly, there is an interest in using CBD, cannabidiolic acid (CBDA) or cannabinoid-rich hemp products in the treatment of idiopathic epilepsy in dogs. We aimed to examine a small cohort in a pilot investigation using a CBD and CBDA-rich hemp product for the treatment of refractory epileptic seizures in dogs. Fourteen dogs were examined in a 24-week randomized cross-over study being provided placebo or CBD/CBDA-rich hemp extract treatment at 2 mg/kg orally every 12 h for each 12-week arm of the study. Serum chemistry, complete blood counts, serum anti-seizure medication (ASM) concentrations and epileptic seizure frequency were followed over both arms of the cross-over trial. Results demonstrated that besides a mild increase in alkaline phosphatase, there were no alterations observed on routine bloodwork at 2, 6, and 12 weeks during either arm of the study. Epileptic seizure frequency decreased across the population from a mean of 8.0 ± 4.8 during placebo treatment to 5.0 ± 3.6 with CBD/CBDA-rich hemp extract (P = 0.02). In addition, epileptic seizure event days over the 12 weeks of CBD/CBDA-rich hemp treatment were 4.1 ± 3.4, which was significantly different than during the 12 weeks of placebo treatment (5.8 ± 3.1; P =0.02). The number of dogs with a 50% reduction in epileptic activity while on treatment were 6/14, whereas 0/14 had reductions of 50% or greater while on the placebo (P = 0.02). No differences were observed in serum zonisamide, phenobarbital or bromide concentrations while on the treatment across groups. Adverse events were minimal, but included somnolence (3/14) and transient increases in ataxia (4/14) during CBD/CBDA-rich hemp extract treatment; this was not significantly different from placebo. This further indicates that providing CBD/CBDA-rich hemp extract during refractory epilepsy (only partially responsive to ASM), in conjunction with other ASM appears safe. Based on this information, the use of 2 mg/kg every 12 h of a CBD/CBDA-rich hemp extract can have benefits in reducing the incidence of epileptic seizures, when used concurrently with other ASMs.

Treatment of Canine Idiopathic Epilepsy - Clinical Picture after Drug Interaction

Background: The large number of diseases demand perennial development of the pharmaceutical industry. The drug-testing phase is essential to make them available safely. Awareness of pharmacological properties, adverse effects and drug interactions is required. Drug interactions are common in veterinary medicine and should be avoided. At times, epileptic seizures require polydrug therapy, predisposing patients to drug interactions. The interaction between carbamazepine and phenobarbital reported in the literature is an example. The aim of this paper is to report a clinical picture of drug interaction in the treatment of idiopathic epilepsy. Case: A 1-year-old Border Collie male dog, was admitted at the Veterinary Hospital of the Federal University of Lavras in post-ictal. The tutor reported that a year ago the animal had epileptic seizures and clusters with intervals of 21 to 25 days. Despite the continued use of previously prescribed phenobarbital (7.4 mg/kg, v.o., BID, until new recommendations) and carbamazepine (7.5 mg/kg, v.o., BID, until new recommendations), seizure control was not achieved. The physical examination indicated, tachypnea, ptialism, mydriasis, intense fatigue, and alienation from the environment. The patient did not respond to the threat-reflex test. Blood count, hepatic and renal blood chemistry, serum electrolyte (potassium, sodium, calcium and phosphorus), and phenobarbital dosages were requested. Based on the animal's history, breed characteristics, and alterations in the physical examination associated with normal results in complementary exams, idiopathic epilepsy was diagnosed. After analyzing the case, it was observed that the inefficiency in the control of seizures was possibly due to the drug interaction between phenobarbital and carbamazepine. Carbamazepine and phenobarbital reciprocally reduce their half-lives. To confirm the raised hypothesis, the serum concentration of carbamazepine was gradually reduced through weaning from its dose administered to the patient. Serial dosage of the concentration of phenobarbital in the bloodstream was performed. As a result, the serum phenobarbital, previously dosed at a concentration of 13.3 mg/dL with concomitant administration of carbamazepine, increased to 22 mg/dL 40 days after the beginning of weaning from carbamazepine (T0), and then to 36 mg/dL 100 days after T0. There was an increase in the concentration of phenobarbital in the bloodstream while the serum concentration of carbamazepine declined. The patient spaced out his seizures to every 50 to 60 days with phenobarbital monotherapy at a dose of 6 mg/kg. Discussion: Efficient control of clusters, such as the reduction of seizures by 50%, was only possible due to the meticulous perception of the possible interaction reported in medicine. Carbamazepine and phenobarbital are P450 isoenzyme inducers. The concomitant administration of both drugs potentiated the action of isoenzymes in the hepatic microsomal system, which led to an accelerated metabolic processing of the drugs. After weaning from carbamazepine, that is, reducing the action of carbamazepine on the isoenzymes of the P450 enzyme system, the concentration of phenobarbital normalized at 36 mg/dL. Such concentration is within the reference range reported in the literature: 25 mg/dL to 35 mg/dL of serum phenobarbital for treatment efficacy. Therefore, the control of convulsive crises was achieved. The increase in the concentration of phenobarbital due only to weaning from carbamazepine, even after decreasing the daily dose of barbiturate prescribed to the animal, contributed to evidence of the interaction of these drugs. It is noted that prior knowledge of pharmacological properties, careful study of the patient's history, and the cooperation of the tutor were essential for the therapeutic success and practice of evidence-based veterinary medicine. Keywords: drug interaction, carbamazepine, phenobarbital, P450 enzyme. Título: Tratamento da epilepsia idiopática canina - quadro clínico após interação medicamentosa. Descritores: interação medicamentosa, carbamazepina, fenobarbital, enzima P450.

Therapeutic Aspects of Dogs with Presumptive Diagnosis of Idiopathic Epilepsy

Background: Epilepsy is a chronic neurological condition characterised by recurrent epileptic seizures. Various antiepileptic drugs are used for the management of canine idiopathic epilepsy. Phenobarbital is the drug of choice for long-term treatment in dogs. Although it is well tolerated, phenobarbital can cause liver injury if administered alone or in combination with other drugs. Therefore, the main of this study was to identify dogs with presumptive diagnosis of idiopathic epilepsy and information about the antiepileptic drugs, the dose and frequency of administration, period of treatment, frequency of the seizure before and after start the treatment, complementary exams and adverse effects.Materials, Methods & Results: In this study were included 21 dogs with idiopathic epilepsy. All dogs were examined and having blood taken for blood count, biochemical tests (ALT, AST, AP, total protein, albumin, creatinine, urea, amylase, lipase, cholesterol and triglycerides), measurement of serum phenobarbital and/or potassium bromide and, some dogs, free T4 by dialysis and canine TSH. In this study, it was observed monotherapy (phenobarbital) in 76.19% (16/21), double therapy (phenobarbital and potassium bromide) in 19.05% (4/21) and triple therapy (phenobarbital, potassium bromide and gabapentin) in 4.76% (1/21) of dogs. The phenobarbital was used as monotherapy with dose between 1.4 and 12 mg kg-1 and the median of serum concentration was 26.41 μg kg-1. There was significant reduction in the frequency of the seizure after start the treatment. There was refractory to antiepileptic drugs in two dogs (9.5%). In blood analysis, there was increase serum activities of AP (23.81%) and ALT (14.20%), decrease total protein (42.29%), hypoalbuminemia (9.5%) and it was not increased AST activities. The main adverse effects were nodularliver damage and hypothyroidism.Discussion: In most cases of dogs with idiopathic epilepsy, monotherapy is preferred, because it tends to avoid complications that may arise from drug interactions and may also improve compliance by providing a simple treatment regimen. In this study, the phenobarbital controlled the seizures when used as monotherapy. It is considered success of an antiseizure drug when there is a reduction of seizure frequency by at least 50%, with minimal drug side effects. Approximately 20-30% of dogs with epilepsy do not have satisfactory seizure control or experience intolerable adverse effects with appropriate conventional medical treatment. In this study, there was refractory to antiepileptic drugs in 9.5%, one dog treated with phenobarbital and other with phenobarbital and potassium bromide. The long-term use of phenobarbital causes increase in liver enzymes, ALT and, mainly, ALP, these are attributed to enzymatic induction and to low degree of liver damage. ALT and AP increased the values and this does not necessarily indicate clinically significant liver damage or the need to stop therapy. The risk of liver toxicity appears to be greater with concentrations higher than 35 μg mL-1 or when multiple potentially hepatotoxic drugs are used. Other factors associated to the long-term use of anticonvulsant, such phenobarbital, potassium bromide or both, for the treatment of idiopathic epilepsy in dogs is acute pancreatitis and hypothyroidism. In this study, it was not observed acute pancreatitis, but there were two dogs with hypothyroidism. The long-term use of phenobarbital did not cause significant side effects, even with changes in the biochemical tests.

Investigating the potential of the anti-epileptic drug imepitoin as a treatment for co-morbid anxiety in dogs with idiopathic epilepsy

BackgroundBehavioural changes associated with idiopathic epilepsy (IE) have been identified in dogs, with fear and anxiety-related problems seen in both drug-naïve dogs and dogs treated with anti-epileptic drugs (AEDs). Treating anxiety-related behaviour in dogs with IE may be challenging, as seizures are a contraindication for many conventional anxiolytic drugs. In addition, many dogs with IE are already treated with AEDs to reduce their seizure frequency, which may have negative effects if used in polytherapy. Imepitoin is low-affinity partial agonist at the benzodiazepine (BDZ) site of the GABAA receptor, and has been demonstrated to have both anticonvulsant and anxiolytic effects in laboratory rodents. Imepitoin has been developed for the treatment of IE in dogs, with demonstrated anticonvulsant effects and high tolerability and safety. To date, imepitoin’s potential to reduce anxiety in dogs with IE has not been investigated. An online survey was conducted to investigate the effect of imepitoin on fear and anxiety-related behaviours in dogs with IE. Eighty-five valid responses were received from owners of dogs with IE currently treated with imepitoin. Anxiety-related behaviour was quantified before and during imepitoin treatment using a validated questionnaire tool (C-BARQ).ResultsNo differences were observed in the five fear/anxiety-related measures between the two time periods (before vs. during treatment) for dog directed fear, stranger directed fear, non-social fear, pain sensitivity and separation related behaviour. A median 45% reduction in seizure frequency/month was observed following imepitoin treatment; however, imepitoin did not appear effective in reducing seizure frequency in a minority of cases. Polyphagia was the most common chronic side effect, and more side effects were reported in polytherapy cases.ConclusionsImepitoin does not appear to improve anxiety-related behaviour in dogs with IE treated with this medication for its anti-epileptic effects. Investigating the effects of imepitoin upon the behaviour of dogs with recognised behavioural anxiety-related problems (e.g. specific fears and phobias, separation related behaviours), in both healthy dogs and dogs with epilepsy is required to further explore any potential anxiolytic effects of this medication.

Treatment in canine epilepsy--a systematic review.

BackgroundVarious antiepileptic drugs (AEDs) are used for the management of canine idiopathic epilepsy (IE). Information on their clinical efficacy remains limited. A systematic review was designed to evaluate existing evidence for the effectiveness of AEDs for presumptive canine IE. Electronic searches of PubMed and CAB Direct were carried out without date or language restrictions. Conference proceedings were also searched. Peer-reviewed full-length studies describing objectively the efficacy of AEDs in dogs with IE were included. Studies were allocated in two groups, i.e. blinded randomized clinical trials (bRCTs), non-blinded randomized clinical trials (nbRCTs) and non-randomized clinical trials (NRCTs) (group A) and uncontrolled clinical trials (UCTs) and case series (group B). Individual studies were evaluated based on the quality of evidence (study design, study group sizes, subject enrolment quality and overall risk of bias) and the outcome measures reported (in particular the proportion of dogs with ≥50% reduction in seizure frequency).ResultsTwenty-six studies, including two conference proceedings, reporting clinical outcomes of AEDs used for management of IE were identified. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. Only four bRCTs were identified in group A and were considered to offer higher quality of evidence among the studies. A good level of evidence supported the efficacy of oral phenobarbital and imepitoin and fair level of evidence supported the efficacy of oral potassium bromide and levetiracetam. For the remaining AEDs, favorable results were reported regarding their efficacy, but there was insufficient evidence to support their use due to lack of bRCTs.ConclusionsOral phenobarbital and imepitoin in particular, as well as potassium bromide and levetiracetam are likely to be effective for the treatment of IE. However, variations in baseline characteristics of the dogs involved, significant differences between study designs and several potential sources of bias preclude definitive recommendations. There is a need for greater numbers of adequately sized bRCTs evaluating the efficacy of AEDs for IE.

Study on the correlation between serum homocysteine levels with pediatric idiopathic epilepsy

Objective To study the clinical significance of determination on homocysteine in serum of pediatric idiopathic epilepsy. Methods The homocysteine level in serum of 81 patients with pediatric idiopathic epilepsy was determined,and the value of normal children was tested and compared as control. Results The concentration of Hey in research group was from 7.6mol/L to 22.0μmol/L,the mean value was(15.91 ±2.38)μmol/L,The concentration of Hcy in control group was from 3μmol/L to 9μmol/L,and the mean value was(6.87 ± 1.75)μmol/L.which showed a significant difference(P＜0.05).By comparison,the high concentration(＞15 μmol/L)of Hcy in control group was only 6 cases,while it was 73 cases in research group,which also showed a significant difference (P＜0.05). Conclusion Hcy level was apparently relevant with occurring rate of pediatric idiopathic epilepsy.In the diagnosed clinical treatment of idiopathic epilepsy,the closely monitor of serum level of homocysteine,and timely promoting Hcy metabolism.should be carried out. Key words: Homocysteine; Pediatric,idiopathic,epilepsy

PELLAGRA-LIKE SKIN LESIONS DUE TO THE KETOGENIC DIET

It is my belief that the following case report constitutes an illustration of one of the dangers in the use of the ketogenic diet in the treatment of idiopathic epilepsy: REPORT OF CASE Mrs. H. E. R., an American, aged 33, 5 feet 4 inches (163 cm.) tall, weighing 112 pounds (50.8 Kg.), came to the clinic complaining of attacks of convulsions, lasting from fifteen to twenty minutes, followed by stupor. She cried easily and was nervous and excitable; her memory was poor and she was not able to concentrate. The attacks of convulsions had begun four years before, appearing three weeks after the birth of a child. Following the first convulsion she had been unconscious for six hours. She had had these attacks frequently, having as many as two or three a day, until she became pregnant again a little more than two years before; during this pregnancy she

Treatment of Idiopathic Epilepsy by Induced Malaria

The use of malaria as a therapeutic agent in epilepsy was suggested by the known beneficial effects of other specific infections in this disorder. The earliest observation was probably that of Plato, who found that lepers were free from convulsions. A “tendency to respite which is sometimes temporarily induced in the course of the confirmed disease” (by febrile infections) is noted by Aldren Turner (1). Hamilton (2) found that of 11 cases who contracted typhoid 9 showed distinct temporary improvement, and 1 of these was free from seizures for four years. Maisonneuve and Gerard (3) reported cases of epilepsy whose seizures ceased altogether during 2 attacks of intermittent fever.

Influence of Acid-Forming and Base-Forming Constituents of Ketogenic Diet Used in Treatment of Idiopathic Epilepsy.

Influence of Acid-Forming and Base-Forming Constituents of Ketogenic Diet Used in Treatment of Idiopathic Epilepsy.

Treatment of Idiopathic Epilepsy by Appendicostomy for Colonic Irrigation

Treatment of Idiopathic Epilepsy by Appendicostomy for Colonic Irrigation

An Inquiry into the Efficacy of Digitalis in the Treatment of Idiopathic Epilepsy

An Inquiry into the Efficacy of Digitalis in the Treatment of Idiopathic Epilepsy