Long-term seizure remission in childhood absence epilepsy: might initial treatment matter?

Examine the possible association between long-term seizure outcome in childhood absence epilepsy (CAE) and the initial treatment choice.

Children with CAE were prospectively recruited at initial diagnosis and followed in a community-based cohort study. Children presenting with convulsive seizures, significant imaging abnormalities, or who were followed <5 years were excluded. Early outcomes included success of initial medication, early remission, and pharmacoresistance. The primary long-term outcome was complete remission: ≥5 years both seizure free and medication free. Survival methods were used for analyses.

The first medication was ethosuximde (ESM) in 41 (69%) and valproic acid (VPA) in 18 (31%). Initial success rates were 59% (ESM) and 56% (VPA). Early remission and pharmacoresistance were similar in each group. Apart from atypical electroencephalography (EEG) features (61% [VPA], 17% [ESM]), no clinical features varied substantially between the treatment groups. Complete remission occurred in 31 children (76%) treated with ESM and 7 (39%) who received VPA (p = 0.007). Children with versus without atypical EEG features were less likely to enter complete remission (50% vs. 71%, p = 0.03). In a Cox regression, ESM was associated with a higher rate of complete remission than VPA (hazards ratio [HR] 2.5, 95% confidence interval [CI] 1.1-6.0; p = 0.03). Atypical EEG features did not independently predict outcome (p = 0.15). Five-year and 10-year remission, regardless of continued treatment, occurred more often in children initially treated with ESM versus VPA.

These findings are congruent with results of studies in genetic absence models in rats and provide preliminary evidence motivating a hypothesis regarding potential disease-modifying effects of ESM in CAE. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.