Abstracts

Rationale: Lennox-Gastaut Syndrome (LGS) is a severe, often treatment-resistant form of epilepsy characterized by the triad of multiple seizure types, cognitive impairment, and a slow spike and wave pattern on EEG. These features frequently emerge separately over time. The diagnosis is typically made before age 8. During those years of evolution to LGS, many children have a period of seizure freedom. This time may represent an underexplored opportunity to modify the natural history of LGS through preventive therapies. However, the details and circumstances of those seizure gaps are under-described. The current study aims to examine the evolution of LGS over the first five years of life in order to identify a potential time for intervention to prevent progression of encephalopathy. Methods: We reviewed charts of children diagnosed with LGS using the Rare Epilepsies in New York City (RENYC) database, which includes neurology notes written between 2010 - 2014 from five academic centers in New York City. The LGS diagnosis was confirmed through consensus review of charts by three independent reviewers. In order to focus on the early evolution of LGS in detail, we examine children who turned 5 in 2014. For children who met those criteria, the dates of important events were collected by chart abstraction, including first seizure, first tonic seizure, slow spike and wave on EEG, EMU visits, and hospitalizations. Seizure free periods were defined as greater than 30 days without unprovoked seizures and were recorded as the first day of that 30-day period of known seizure freedom to the day seizures recurred. Results: Twenty-five children turned 5 in 2014 and had a confirmed diagnosis of LGS (see table 1). Median onset of seizures from birth was 5 (IQR 3 – 16) months and median onset of a slow spike and wave in EEG reports was 25 (14 – 40] months. All children were developmentally delayed. Four children did not have enough information in their charts to collect event dates or seizure frequency and another four had event dates but no seizure frequency described. Five children had no seizure free period. Twelve had at least one gap (see Figure 1). In these 12, the median length of longest gap was 13.5 (8 – 20.5) months. Compared to children with no gap, these 12 had the first seizure at a younger age (with gap, median 3.5 [3 – 5.75] months vs no gap, 9 [3 – 32] months; p=0.4) and a shorter time from birth to slow spike and wave on EEG (16.5 [11.5 – 24.5] months vs 36 [35 – 41] months; p=0.06). Eight of the 12 children with gaps had the onset of a slow spike and wave on EEG prior to their period of seizure freedom. Conclusions: Half of children with LGS in our cohort had a period of seizure freedom. Of these, two thirds had slow spike and wave shortly before the seizure gap began. This observation raises the possibility that, for some children, new onset slow spike-and-wave heralds future intractability, despite occurring just prior to a brief period of seizure quiescence. This may represent an ideal time to intervene with the intention of preventing deterioration into epileptic encephalopathy. In our ongoing work, we are examining four- and six-year-olds in the identified LGS cohort to verify and expand on these initial observations. Funding: No funding