Objective Whether febrile status epilepticus (FSE) produces hippocampal sclerosis (HS) and temporal lobe epilepsy (TLE) has long been debated. Our objective is to determine if FSE produces acute hippocampal injury that evolves to HS. Methods FEBSTAT and two affiliated studies prospectively recruited 226 children aged 1 month to 6 years with FSE and controls with simple febrile seizures. All had acute MRIs and follow-up MRIs were obtained at approximately 1 year later in the majority. Visual interpretation by two neuroradiologists informed only of subject age was augmented by hippocampal volumetrics, analysis of the intra-hippocampal distribution of T2 signal, and apparent diffusion coefficients. Results Hippocampal T2 hyperintensity, maximum in Sommer's sector, occurred acutely after FSE in 22 of 226 children in association with increased volume. Follow-up MRIs obtained on 14 of the 22 with acute T2 hyperintensity showed HS in 10 and reduced hippocampal volume in 12. In contrast, follow-up of 116 children without acute hyperintensity showed abnormal T2 signal in only 1 (following another episode of FSE). Furthermore, compared to controls with simple febrile seizures, FSE subjects with normal acute MRIs had abnormally low right to left hippocampal volume ratios, smaller hippocampi initially and reduced hippocampal growth. Interpretation Hippocampal T2 hyperintensity after FSE represents acute injury often evolving to a radiological appearance of HS after one year. Furthermore, impaired growth of normal appearing hippocampi after FSE suggests subtle injury even in the absence of T2 hyperintensity. Longer follow-up is needed to determine the relationship of these findings to TLE.

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Summary:Purpose: To investigate whether lamotrigine (LTG) monotherapy is effective and safe for newly diagnosed typical absence seizures in children and adolescents (aged 3-15 years, n = 45).Methods: A "responder-enriched" study design was used: open-label dose escalation was followed by placebo-controlled, double-blind testing of LTG. Conventional hyperventilation testing with EEG recording was used to confirm diagnoses and assess treatment success defined as complete freedom from seizures. Ambulatory 24-h EEG recordings provided supporting evidence of effectiveness. Safety was assessed by evaluation of adverse events, vital signs, and physical, neurologic, and laboratory examinations. Plasma samples were taken to evaluate the pharmacokinetics of LTG. Results:During initial open-label dose escalation, 71.4% of patients (intent-to-treat) or 82% (per protocol analysis) became seizure free; individual patients responded at doses ranging from 2 to 15 mg/kg/day (median, 5.0). In the placebocontrolled, double-blind phase of the study, statistically significantly more patients remained seizure free when treated with LTG (62%) than with placebo (21%; p < 0.02; for the intentto-treat analysis). Mean plasma concentrations of LTG, were linearly related to dose, although there was substantial interindividual variation. No patients were withdrawn from the study for any safety-related reason.Conclusions: LTG monotherapy is effective for typical absence seizures in children and is generally well tolerated. Key Words: Lamotrigine-Pediatric-Absence seizuresEfficac y-Tolerability .Typical absence seizures (TASs) account for -13-24% of all epilepsy in children and adolescents (1). The seizures involve brief loss of awareness, responsiveness, and memory, and are accompanied by regular and symmetric 3-Hz spike and slow wave discharges in EEG recordings (2,3). Current therapies for TASs include ethosuximide (ESM) and valproic acid (VPA), both of which are highly effective. However, ESM has little efficacy for other types of seizures, and VPA, especially in children, has been associated with hepatic and hematologic adverse effects, weight gain, hair loss, and tremor.Lamictal (lamotrigine; 6-(2,3-dichloropheny1)-1,2,4-triazine-3,5-diamine) is chemically unrelated to any