The prognostic significance of initial antiepileptic drug (AED) failure in children with absence epilepsy was studied at the IWK-Grace Health Center, Dalhousie University, Halifax, Nova Scotia, Canada. Patients were identified by review of centralized EEG records, and follow-up was conducted by parent mail-in questionnaire or physician review of records. Of 86 patients followed for >24 months (median 171 months), 52 (60%) responded to the initial AED with complete seizure control for >1 year before final follow-up. Of 22 initially treated with valproate (VPA), 17 (77%) responded compared with 35 (55%) of 64 treated with either ethosuximide (32 of 59) or clonazepam (3 of 5) (p=0.07). Final remission rate was 69% when the initial AED was successful compared to 41% when it failed (p<0.02). Other seizure types (generalized tonic-clonic or myoclonic) coexisting before or during initial AED treatment were risk factors for a lower response rate. Patients whose initial treatment failed were more likely to develop juvenile myoclonic epilepsy (32% cf 10%; p<0.02) and intractable epilepsy (17% cf 2%; p<0.04). 
COMMENT. The initial AED treatment of absence epilepsy is successful in 60% of children. Ethosuximide is favored as the initial treatment of choice but the response rate to valproate is greater. Risk factors for a lower final remission rate include failure of the initial AED and coexisting generalized tonic-clonic or myoclonic seizures. Poor response to the initial therapy is also predictive of progression to juvenile myoclonic or intractable epilepsy.
Similar conclusions were reported following a meta-analysis study of 2303 patients from 26 publications of 23 cohorts conducted at Leiden University Hospital, The Netherlands (see Progress in Pediatric Neurology III, PNB Publishers, 1997;pp60-62) . The poorest outcomes occurred in patients who developed generalized tonic-clonic seizures (GTCS) and in those with the longest follow-up. In long-term follow-up of absence epilepsy (AE) patients, the incidence of GTCS was 50%. Of those with AE and GTCS, 35% were seizure free, whereas in the 50% with AE uncomplicated by GTCS, 78% were seizure free.