This study provides Class II evidence that clobazam as adjunctive therapy is efficacious, in a dosage-dependent manner, in reducing mean weekly drop seizure rates of patients with LGS over 12 weeks.

Summary:Purpose: To present the results of transcallosal surgical resection of hypothalamic hamartoma (HH) in 26 patients with refractory epilepsy in a prospective outcome study.Methods: Patients with refractory epilepsy symptomatic to HH were referred for surgical resection of their HH (mean age, 10.0 years; range, 2.1-24.2 years). A transcallosal, interforniceal approach was used to remove and/or disconnect the hamartoma. Volumetry was obtained on pre-and postoperative brain MRI scans to determine percentage of resection. Outcome assessment included determination of postoperative seizure frequencies in comparison to baseline and the incidence of postoperative complications. Postoperative changes in cognitive and behavioral functioning, in comparison to baseline, were elicited by parental report.Results: The average postoperative follow-up interval was 20.3 months (range, 13-28 months). Fourteen (54%) patients were completely seizure free, and nine (35%) had at least a 90% improvement in total seizure frequency. Parents reported postoperative improvement in behavior in 23 (88%) patients and in cognition in 17 (65%) patients. Transient postoperative memory disturbance was seen in 15 (58%) patients, but persisted in only two (8%). Two (8%) patients had persisting endocrine disturbance requiring hormone replacement therapy (diabetes insipidus and hypothyroidism in one each). With univariate analysis, the likelihood of a seizure-free outcome correlated with younger age, shorter lifetime duration of epilepsy, smaller preoperative HH volume, and 100% HH resection.Conclusions: Refractory epilepsy associated with HH can be safely and effectively treated with surgical resection by a transcallosal, interforniceal approach. Short-term memory deficits appear to be transient for most patients, and family perception of the impact of surgery on cognitive and behavioral domains is favorable. Complete resection yields the best result.

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...