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Objective: To review our clinical experience with intravenous (iv) lacosamide (LCM) in children less than 12 years old., Background: Use of LCM to treat children with epilepsy has been supported by multiple studies with limited information on iv use in children., Designs/methods: All children given iv LCM were identified from 2009 to 2015. Records were audited for demographics, seizure classification, etiology, EEG, imaging, indication. Baseline seizure frequency was based on parental reporting, continuous video EEG and direct observation., Results: 47 patients were identified with median age 6.5 years, 18 less than 3 years old, including 8 younger than 12 months. LCM was an adjunctive therapy of ≥2 antiepileptic drugs (AEDs). LCM was administered intravenously to treat epilepsia partialis continua (n = 3, dose range 5-10 mg/kg), status epilepticus (n = 11, median dose 7.2 mg/kg, range 4-11 mg/kg), and acute exacerbation of seizure frequency (n = 18, median dose 4.5 mg/kg, range 1-11 mg/kg). Parenteral form was substituted for oral form for 10 children treated with maintenance LCM unable to ingest/tolerate enteral medication and 5 who were given iv LCM to initiate maintenance treatment (median dose 4 mg/kg, range: 2-10 mg/kg). The infusion was effective for 24 out of 37 children (65%) naive to LCM. Sedation (one with ataxia) was noted in 5/36 children (14%), without any other identified adverse events., Conclusion: This is the first published retrospective study of very young critically ill children receiving iv LCM. The acute tolerability at this dosing range represents a positive trend and need confirmation from larger studies., (Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Purpose: This randomized, double-blind, dose-ranging study evaluated safety and efficacy of clobazam (CLB) as adjunctive therapy for drop seizures in patients with Lennox-Gastaut syndrome (LGS)., Methods: Sixty-eight patients with LGS aged 2-26 years were administered CLB (low dose = target 0.25 mg/kg/day; high dose = target 1.0 mg/kg/day). The study consisted of 4-week baseline, 3-week titration, and 4-week maintenance periods, followed by a 3-week taper or continuation in an open-label study. Seizure frequency was recorded in a diary by the parent/caregiver throughout the study., Results: Weekly drop seizure rates were significantly reduced from baseline in both the high-dose and low-dose groups; the reduction was significantly greater in the high-dose group. A significantly greater proportion of patients in the high-dose group experienced reductions in drop seizures of >or=25%, >or=50%, and >or=75% compared to the low-dose group; more patients in the high-dose group experienced a 100% reduction, but the difference was not significant. Nondrop seizures were also reduced in a dose-dependent manner. In both investigator and parent/caregiver global evaluations, patients in the high-dose group showed significantly greater improvements in overall symptoms compared to low-dose CLB. Adverse events were generally mild or moderate, and were similar between dose groups. Five serious adverse events were reported in four patients, but in no case was CLB discontinued., Conclusions: Clobazam was well tolerated and reduced drop seizure rates; high-dose CLB was more effective than low-dose CLB. Other seizure types were also reduced.

Purpose: To assess the efficacy and safety of levetiracetam (LEV) as adjunctive therapy in children with treatment-resistant partial-onset seizures., Methods: Children (aged 6-12 years) with treatment-resistant partial-onset seizures receiving one standard antiepileptic drug (AED) were eligible. After a 4-week baseline period, children received LEV in a 6-week titration phase (target dose, 40 mg/kg/day) followed by an 8-week evaluation phase. Seizure frequency during the evaluation period with individualized LEV doses (20-40 mg/kg/day) were compared with the 4-week baseline seizure frequency. Plasma concentrations of LEV and other AEDs were determined to evaluate potential drug interactions., Results: Twenty-four subjects enrolled and received LEV; 23 entered the evaluation phase, and 22 completed the evaluation phase. Compared with their baseline seizure frequency, 12 (52%) of 23 subjects entering the evaluation phase had their seizure frequency decrease by >50%. Two subjects remained seizure free during the entire evaluation period. LEV did not significantly affect plasma concentrations of any concomitant AED during this study, and no alteration of mean clinical laboratory values was observed. The most commonly reported adverse events were headache, infection, anorexia, and somnolence., Conclusions: This open-label study of adjunctive LEV therapy (at 20-40 mg/kg/day) suggests that LEV is effective, safe, and well tolerated in children ages 6-12 years with treatment-resistant partial-onset seizures. A randomized, placebo-controlled, double-blind trial of LEV adjunctive therapy in children with treatment-resistant partial-onset seizures is needed and ongoing to confirm these open-label findings.

Purpose: The pharmacokinetics of the novel antiepileptic drug (AED) levetiracetam and its major metabolite, ucb L057, were studied in children with partial seizures in a multicenter, open-label, single-dose study., Methods: Twenty-four children (15 boys, nine girls), 6 to 12 years old, received a single dose of levetiracetam (20 mg/kg) as an adjunct to their stable regimen of a single concomitant AED, followed by a 24-h pharmacokinetic evaluation., Results: In children, the half-lives of levetiracetam and its metabolite ucb L057 were 6.0 +/- 1.1 and 8.1 +/-2.7 hours, respectively. The Cmax and area under the curve (AUC) of levetiracetam equated for a 1-mg/kg dose were lower in children (Cmax, norm=1.33 plus minus 0.35 microg/ml; AUCnorm=12.4 +/- 3.5 microg/h/ml) than in adults (Cmax, norm=1.38 +/- 0.05 microg/ml; AUCnorm=11.48 +/- 0.63 microg/h/ml), whereas the renal clearance was higher. The apparent body clearance (1.43 +/- 0.36 ml/min/kg) was approximately 30-40% higher in children than in adults. Levetiracetam was generally well tolerated., Conclusions: On the basis of these data, a daily maintenance dose equivalent to 130-140% of the usual daily adult maintenance dosage (1,000-3,000 mg/day) in two divided doses, on a weight-normalized level (mg/kg/day) is initially recommended. Clinical efficacy trials in children are ongoing with dosages of 20 to 60 mg/kg/day.

The medical records of 27 children admitted to the MINCEP Epilepsy Program for evaluation of intractable epilepsy but later shown to have nonepileptic events by EEG with simultaneous video monitoring were reviewed. Four groups were identified: pure psychogenic events (5 patients), psychogenic events plus epileptic seizures (3 patients), pure nonepileptic physiologic events (5 patients), and nonepileptic physiologic events plus seizures (14 patients). Historical data, physical examinations, and neurodiagnostic evaluations (including previous EEGs, neuroradiologic evaluations, and neuropsychologic testing) were reviewed. Children in all groups, except for those with pure psychogenic seizures, had a history of multiple seizure types identified by parents or caretakers. A history of status epilepticus was obtained in 64% (of 22 patients), including 11 of 14 patients with physiologic events plus seizures. Abnormal findings on neurologic examination were common, especially in children with nonepileptic physiologic events. All but two patients had a history of interictal epileptiform abnormalities on previous routine EEGs. Based on identification of nonepileptic events, antiepileptic drugs (AEDs) were discontinued completely in eight patients (30%) and the total number of AEDs was reduced in nine others (33%). A diagnosis of nonepileptic events should be considered in all children with refractory seizures or multiple seizure types. Abnormal findings on routine (interictal) EEG may actually confound the diagnosis. Intensive neurodiagnostic EEG-video recording is the preferred method for distinguishing nonepileptic from epileptic seizures.

In a retrospective study, records of 46 patients (24 women and 22 men aged 17-51 years; mean 29.2 years), who had been treated with ethotoin (EHN) as adjunctive therapy for control of intractable seizures were reviewed. Overall, approximately 51% of this highly selected patient population had a reduction greater than 50% in overall seizure frequency 1 month after initiation of treatment. This was reduced to approximately 25% for the last 3 months of follow-up (mean follow-up period 10.6 months). Tonic seizure frequency was reduced most dramatically, by greater than 50%, in 60% of patients at 1 month and in 35% of patients for the last 3 months of follow-up. This study suggests that prospective controlled trials of EHN, especially for tonic seizures, are needed.

Two independently biologically active compounds, periplanone A and periplanone B can be isolated from fecal material of the American cockroach,Periplaneta americana. In fecal material these occur in a ratio of 1 ∶ 10 while, in intestinal tracts only periplanone B has been found. The latter has been identified as (1Z,5E)-1,10(14)-diepoxy-4(15),5-germacradien-9-one; the identification was confirmed by synthesis. Only the CD (-) enantiomer (1R,2R,5E,7S,10R) exhibited activity. The lower threshold of activity of both natural and synthetic CD (-) pheromone, is 10(-6)-10(-7) μg. Periplanone A has been identified (apart from its stereochemical configuration) as 7-methylene-4-isopropyl-12-oxa-tricyclo[4.4.2.0(1,5)]-9-dodecen-2-one). The structure of this rather unstable compound could be deduced by comparing its NMR, UV, IR, and mass spectra with the NMR and mass spectra of its rearrangement product. Both structures still require confirmation by synthesis, but their spectral data are in complete agreement with the proposed structures. The presence of only periplanone B in the gut and the presence of both periplanone A and periplanone B in the feces suggests that periplanone B is a genuine sex pheromone, whereas peri-planone A might be a biologically active transformation product, which in turn can isomerize into a more stable, but inactive compound.

Both cis-9-and cis-11-tetradecenyl acetate were isolated from 2500 virgin females of the summer fruit tortrix moth Adoxophyes orana (F.v.R.) by gel permeation, column chromatography on silica gel, and gas chromatography. Their chemical, physical, and biological properties were identical to those of the synthetic compounds. In contrast to the single compounds, mixtures of these pheromones were highly active in laboratory and field tests. Catches, in traps, with the pheromone mixture were comparable to those obtained when live females were used as bait. This is the first example of a member of the lepidoptera in which the presence of two isomers is an absolute requirement for activity in laboratory and in field experiments.

Two tortricid mitoth species, Adoxophyes orana and Clepsis spectrana, utilize the samne two isomers, cis-9- and cis-l1-tetradecenyl acetate, as their sex attractant. Commnlunication between the sexes of each species is separated effectively by a different blendinig of both compounds by the females and a different response to these blends by the males.