Objective: To evaluate the efficacy and tolerability of levetiracetam (LEV) as adjunctive therapy in children (4 to 16 years) with treatment-resistant partial-onset seizures. Methods: This multicenter, randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 14-week double-blind treatment period. During the treatment period, patients received either placebo or LEV add-on therapy and were up-titrated to a target dose of 60 mg/kg/day. Results: One hundred ninety-eight patients (intent-to-treat population) provided evaluable data. The reduction in partial-onset seizure frequency per week for LEV adjunctive therapy over placebo adjunctive therapy was significant (26.8%; p 0.0002; 95% CI 14.0% to 37.6%). A 50% or greater reduction of partial seizure frequency per week was attained in 44.6% of the LEV group (45/101 patients), compared with 19.6% (19/97 patients) receiving placebo (p 0.0002). Seven (6.9%) LEV-treated patients were seizure-free during the entire double-blind treatment period, compared with one (1.0%) placebo-treated patient. One or more adverse events were reported by 88.1% of LEV-treated patients and 91.8% of placebo patients. The most common treatment-emergent adverse events were somnolence, accidental injury, vomiting, anorexia, hostility, nervousness, rhinitis, cough, and pharyngitis. A similar number of patients in each group required a dose reduction or withdrew from the study as a result of an adverse event. Conclusion: Levetiracetam adjunctive therapy administered at 60 mg/kg/day is efficacious and well tolerated in children with treatment-resistant partial seizures.

SUMMARYObjective: To prospectively evaluate the etiology of new-onset infantile spasms and evaluate the yield of genetic and metabolic investigations in those without obvious cause after initial clinical evaluation and magnetic resonance imaging (MRI). Methods: Twenty-one U.S. pediatric epilepsy centers prospectively enrolled infants with newly diagnosed West syndrome in a central database. Etiology and investigations performed within 3 months of diagnosis were documented. Results: From June 2012 to June 2014, a total of 251 infants were enrolled (53% male). A cause was identified in 161 (64.4%) of 250 cases (genetic,14.4%; genetic-structural, 10.0%; structural-congenital, 10.8%; structural-acquired, 22.4%; metabolic, 4.8%; and infectious, 2.0%). An obvious cause was found after initial clinical assessment (history and physical examination) and/or MRI in 138 of 161, whereas further genetic and metabolic studies were revealing in another 23 cases. Of 112 subjects without an obvious cause after initial evaluation and MRI, 81 (72.3%) had undergone genetic testing, which showed a causal abnormality in 23.5% and a variant of unknown significance in 14.8%. Although metabolic studies were done in the majority (serum, 79.5%; urine, 69.6%; and cerebrospinal fluid [CSF], 38.4%), these revealed an etiology in only five cases (4.5%). No correlation was found between type of health insurance (public vs. private) and either genetic or metabolic testing. Significance: Clinical evaluation and MRI provide a specific diagnosis in 55% of children presenting with West syndrome. We propose that a cost-effective workup for those without obvious cause after initial clinical evaluation and MRI includes an array comparative genomic hybridization (aCGH) followed by an epilepsy gene panel if the microarray is not definitive, serum lactate, serum amino acids, and urine organic acids.

and yyOvation Pharmaceuticals, Inc., Deerfield, Illinois, U.S.A. SUMMARYPurpose: This randomized, double-blind, doseranging 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 ‡25%, ‡50%, and ‡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. KEY WORDS: Childhood epilepsy, Drop seizure, Atonic seizure, Akinetic seizure, Catastrophic epilepsy.Lennox-Gastaut syndrome (LGS) is a catastrophic childhood epilepsy characterized by multiple types of seizures and developmental delay. Onset of LGS usually occurs between 3 and 10 years of age, and affects boys more often than girls (Beaumanoir & Dravet, 1992). Typical LGS is described by the presence of the characteristic triad of: (1) tonic axial, atonic, and/or atypical absence seizures; (2) electroencephalography (EEG) abnormalities with bursts of diffuse slow spike-wave pattern of 1.5-2.5 Hz; and (3) impaired intellectual growth (Beaumanoir & Blume, 2002;Crumrine, 2002). Atonic or drop seizures are frequent in LGS and are responsible for most injuries associated with falls. The prognosis for LGS is poor, since the seizures tend to be medically refractory, with only 10% of cases experiencing full seizure remission with available therapies. Most patients experience ongoing cognitive impairment and refractory epilepsy, and some patients experience frequent episodes of status epilepticus (Crumrine, 2002;Markand, 2003 (Markand, 2003).Clobazam (CLB) is a novel 1,5-benzodiazepine that was initially developed as an antianxiety treatment designed to decrease AEs associated with 1,4-benzodiazepines while maintaining efficacy (Chapman et al., 1...