PURPOSE: To assess impact of AED failure for lack of efficacy on long-term outcome in children with generalized epilepsy.

METHODS: Children with generalized epilepsy followed for >2 years after diagnosis were identified from a 30-year database of new-onset pediatric epilepsy in Olmsted County, MN. Clinical details abstracted from the medical record included seizure outcome, use of AEDs and number of AEDs failed for lack of efficacy at final follow-up. An AED was defined as failing for lack of efficacy if seizure control was not achieved despite maximum tolerated dose.

RESULTS: Ninety-six children were identified (51% male). Median age at seizure onset was 7.8 years (IQR 3.6, 13.2). Duration of follow-up was 10.0 years (IQR 4.9, 15.4). A defined electroclinical syndrome was identiifed in 67 (70%). At final follow-up, 65 (68%) were seizure-free for >1 year, 35 (54%) of whom were also off AEDs. Seizure freedom was seen in 44/59 (75%) who failed no AED, 10/20 (50%) who failed one AED and 11/17 (65%) who failed two or more AEDs for lack of efficacy (p=0.12). Predictors against seizure freedom included intellectual disability (p<0.001), lack of febrile seizures (p=0.001), abnormal neurological exam (p=0.03) and prior neonatal seizures (p=0.04).

CONCLUSIONS: While there was a trend for children who had never failed an AED for lack of efficacy to have a higher likelihood of seizure freedom, 57% who had failed medication still achieved this outcome. Prognosis was more concerning for those with intellectual disability, neurological exam abnormalities, prior neonatal seizures or lack of febrile seizures.