ADHD-LIKE BEHAVIOURAL PROFILE IN DOGS WITH IDIOPATHIC EPILEPSY

Item does not contain fulltextPurpose: This study was performed to investigate whether stimulation of endocannabinoid system early after status epilepticus (SE) could prevent or modify the subsequent epileptogenesis. We studied the effect of an agonist of endocannabinoid receptors, WIN-55 212-2, on electrographic features during the latent period of post-SE epileptogenesis in rats. Method: The study was carried out on the lithium-pilocarpine model of temporal lobe epilepsy (TLE). Rats were treated with LiCl (127 mg/kg) 24 hour before administration of pilocarpine (25 mg/kg). SE lasted for 90 minutes and was stopped by injection of pentobarbital (25 mg/kg). WIN-55 212-2 (5 mg/kg) or vehicle (DMSO) was administered 4 hour after the end of SE. Cortical and hippocampal electrographic activity was recorded in awake freely moving rats using NeuroLogger (TSE Systems). Behavior was video-recorded. Data of video-EEG monitoring were analyzed offline; the first 34 hour after SE and two 30 hour records made during the period from day 7 to day 12 after SE were included in the analysis. Results: During the first 34 hour after SE, recurrent generalized seizures appeared on EEG. These seizures included both convulsive seizures and ones without obvious motor manifestations. In the period 7-12 days after SE, such generalized seizures did not occur; however, short (1-3 second) 5 Hz cortical spike-and-wave discharges were observed. These discharges were not associated with motor seizures. Administration of WIN-55 212-2 significantly reduced the total duration of convulsive seizures during the first 34 hour after SE and in addition, suppressed the following development of cortical 5 Hz discharges. Conclusion: Administration of the potent agonist of endocannabinoid receptors WIN-55 212-2 had an anticonvulsive effect during the first 34 hour after SE and suppressed further development of non-convulsive cortical spike-and-wave discharges during the early latent period of epileptogenesis. This study was supported by the Russian Foundation for Basic Research, project no. 14-04-01184.1 p

Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies

In recent years, several genes have been causally associated with epilepsy. However, making a genetic diagnosis in a patient can still be difficult, since extensive phenotypic and genetic heterogeneity has been observed in many monogenic epilepsies. This study aimed to analyze the genetic basis of a wide spectrum of epilepsies with age of onset spanning from the neonatal period to adulthood. A gene panel targeting 46 epilepsy genes was used on a cohort of 216 patients consecutively referred for panel testing. The patients had a range of different epilepsies from benign neonatal seizures to epileptic encephalopathies (EEs). Potentially causative variants were evaluated by literature and database searches, submitted to bioinformatic prediction algorithms, and validated by Sanger sequencing. If possible, parents were included for segregation analysis. We identified a presumed disease-causing variant in 49 (23%) of the 216 patients. The variants were found in 19 different genes including SCN1A, STXBP1, CDKL5, SCN2A, SCN8A, GABRA1, KCNA2, and STX1B. Patients with neonatal-onset epilepsies had the highest rate of positive findings (57%). The overall yield for patients with EEs was 32%, compared to 17% among patients with generalized epilepsies and 16% in patients with focal or multifocal epilepsies. By the use of a gene panel consisting of 46 epilepsy genes, we were able to find a disease-causing genetic variation in 23% of the analyzed patients. The highest yield was found among patients with neonatal-onset epilepsies and EEs