Genetic cause of epilepsy in a Greek cohort of children and young adults with heterogeneous epilepsy syndromes.

We describe a cohort of 10 unrelated Greek patients (4 females, 6 males; median age 6.5 years, range 2-18 years) with heterogeneous epilepsy syndromes with a genetic basis. In these patients, causative genetic variants, including two novel ones, were identified in 9 known epilepsy-related genes through whole exome sequencing. A patient with glycine encephalopathy was a compound heterozygote for the p.Arg222Cys and the p.Ser77Leu AMT variant. A patient affected with Lafora disease carried the homozygous p.Arg171His EPM2A variant. A de novo heterozygous variant in the GABRG2 gene (p.Pro282Thr) was found in one patient and a pathogenic variant in the GRIN2B gene (p.Gly820Val) in another patient. Infantile-onset lactic acidosis with seizures was associated with the p.Arg446Ter PDHX gene variant in one patient. In two additional epilepsy patients, the p.Ala1662Val and the novel non-sense p.Phe1330Ter SCN1A gene variants were found. Finally, in 3 patients we observed a novel heterozygous missense variant in SCN2A (p.Ala1874Thr), a heterozygous splice site variant in SLC2A1 (c.517-2A>G), as a cause of Glut1 deficiency syndrome, and a pathogenic variant in STXBP1 (p.Arg292Leu), respectively. In half of our cases (patients with variants in the GRIN2B, SCN1A, SCN2A and SLC2A1 genes), a genetic cause with potential management implications was identified.

Pediatric Headache and Epilepsy Comorbidity in the Pragmatic Clinical Setting.

INTRODUCTION: Demographic and clinical data were collected from three cross-sectional samples, from the headache and epilepsy clinics according to respective protocols. During structured interviews, we examined the co-occurrence of headaches and epilepsy in children and their families: (1) 172 children from the headache clinic, were questioned for the number and type of epileptic seizures and epilepsy diagnosis. (2) Around 70 children from the epilepsy clinic for the frequency and type of headaches and headache syndrome diagnosis. (3) A total of 149 parents of children with benign childhood epilepsy with centro-temporal spikes (BCECTS) and childhood absence epilepsy (CAE), for the relative frequency of headaches in first- and second-degree relatives. RESULTS: Out of 172, 84 (48.8%) children with headache had a migraine and 60 (34.9%) had tension headaches; 3 children (1.7%) had epilepsy or unprovoked seizures. Migraine and epilepsy, co-occurred in 2/84 (2.3%). Eight out of 70 patients with epilepsy had headaches (11.4%); none had migraine. Around 43% of patients with BCECTS or CAE had a family history of headache, more prevalent in first-degree relatives of children with BCECTS than CAE. CONCLUSION: Contrary to existing literature, migraine and epilepsy, co-occurred infrequently in these highly selected samples. Family history of headache was frequent in patients with BCECTS and CAE, without any significant difference between the two.

Intravenous midazolam in convulsive status epilepticus in children with pharmacoresistant epilepsy.

Although the efficacy of midazolam in refractory status epilepticus and as a first-line agent in children with established status epilepticus has been reported, differences in starting doses, continuation method, timing of efficacy assessment, and discontinuation pose limitations in deriving a specific protocol for midazolam use. An audit of clinical experience with a protocol of midazolam as first-line agent for impending status epilepticus (defined as a continuous, generalized, convulsive seizure lasting >5 minutes) in 76 episodes of unprovoked convulsive status epilepticus in children 1-15 years old with treatment-refractory epilepsy demonstrated that: (1) repeated bolus midazolam 0.1mg/kg (every 5 minutes, maximum 5) controlled 91% of events; (2) three bolus doses controlled 89% of the episodes, with minimal chance of response beyond that; (3) treating impending status resulted in lower doses (mean 0.17 mg/kg) than reported and infrequent utilization of additional anticonvulsants (9%); and (4) adverse events were infrequent (respiratory depression 13%, assisted ventilation 3%).