Abstracts

Rationale:
Lennox-Gastaut Syndrome (LGS) is a refractory epileptic encephalopathy defined by multiple seizure types, cognitive and behavioral impairments, and slow spike-and-wave complexes on EEG (Scheffer et al, Epilepsia 2017). LGS can arise from heterogenous etiologies and accounts for 4% of all cases of childhood epilepsy (Trevathan et al, Epilepsia 1997). To better characterize the development of LGS and identify potential therapeutic windows for treatment, we measured the time intervals between key clinical timepoints and compared LGS time intervals other refractory epilepsy syndromes.
Method:
Using the Informatics for Integrating Biology & the Bedside program (i2b2), we retrospectively screened patients with intractable epilepsy at our center by ICD9 and ICD10 codes. LGS patients were identified based on diagnosis by the treating physician and confirmed clinical criteria (Scheffer et al, Epilepsia 2017). Relevant clinical data were abstracted from the electronic health records, including timepoints (seizure onset, first unprovoked seizure, refractory diagnosis and LGS diagnosis per chart reviewer) and seizure etiology. A set of control subjects with refractory epilepsy (not LGS) were identified from the same patient pool. Comparative analysis used fisher’s exact T-tests and Spearman’s correlation.
Results:
The sample included 36 individuals with LGS (59% M; median current age 11 [interquartile range (IQR) 7-14.5] years) and 18 non-LGS controls (33% M; median current age 46.5 [38-55] years) LGS patients had an earlier age of first unprovoked seizure (LGS median 8 months, [IQR 2-18 months]; non-LGS 216 [168-312], p< 0.01, Figure 1A) and a shorter time interval to a refractory diagnosis than non-LGS controls (LGS median 17 [7-36] months; non-LGS 72 [44.25-133] months, p< 0.01, Figure 1B). There was a positive correlation between the age at seizure onset and age at refractory diagnosis (Figure 2A, rho=0.71, p< 0.01) in the LGS cohort. However, there was no correlation between the age at seizure onset and the time interval to refractory diagnosis in the LGS cohort (rho=0.19, p=0.25; Figure 2B). Shorter time to refractory did not correlate with shorter time to LGS diagnosis (rho=0.31, p=0.06). When comparing the difference in time interval to refractory diagnosis, there was no difference between LGS patients who had a genetic versus structurally acquired etiology (p=0.62).
Conclusion:
Individuals eventually diagnosed with LGS showed a more rapid evolution to refractory epilepsy from their initial seizure onset. Additionally, individuals with LGS had an earlier age of seizure-onset that was not explained by etiology. Since the time from onset of seizures to refractory diagnosis is shorter in LGS than in other epilepsy syndromes, there is a short therapeutic window during which treatments stemming progression to LGS may be effective.
Funding:
:NIH-NINDS K12 (NS066274-10)