Prognostic Significance of Failure of the Initial Antiepileptic Drug in Children with Absence Epilepsy

Abstract

Summary:Purpose: In children with childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE), to determine the impact of failure of initial antiepileptic drug (AED) for lack of efficacy in eventual seizure control and long-term remission of epilepsy.Methods: Centralized EEG records for the province of Nova Scotia allowed identification of all children seen with CAE or JAE between 1977 and 1985. Information regarding success or failure of initial AED in fully controlling seizures and longterm seizure control and remission of epilepsy was collected by patient questionnaire and chart review.Results: Eighty-six of 92 eligible patients were followed up (75 CAE, 11 JAE). Initial AED treatment was successful in 52 (60%) of 86. Success tended to be greater for valproate (VPA) than for other AEDs (p ‫ס‬ 0.07), and lower if generalized tonic-clonic or myoclonic seizures coexisted (p < 0.004 and p < 0.03). Terminal remission was more likely if the initial AED was successful than if it had failed (69% vs. 41%; p < 0.02). Compared with those in whom the initial AED was successful, subjects whose initial AED had failed were more likely to progress to juvenile myoclonic epilepsy (JME) at last follow-up (32% vs. 10%; p < 0.02) and to develop intractable epilepsy (17% vs. 2%; p < 0.04).Conclusions: Initial AED was successful in 60% of children with AE. If the first AED failed, the outcome was less favorable, with a lower rate of terminal remission and a higher rate of progression to JME and intractable epilepsy. Key Words: Childhood absence epilepsy-Juvenile absence epilepsyAntiepileptic drug-Valproic acid.In children with epilepsy, if the initial antiepileptic drug (AED) fails to control seizures, the prognosis for seizure control is often thought to be poor. However, only two studies have looked at this question in the pediatric population. Camfield et al. (1) studied 417 children with partial, primary, and secondarily generalized seizures and found that 17% required a second AED for seizure control. Long-term remission of epilepsy occurred in 61% of children successfully treated with one medication versus only 42% of those requiring more than one AED for seizure control (p < 0.002). A second study looking at 24 children with partial epilepsy found that 29% achieved seizure control with a second AED (2).The prognostic significance of initial AED failure in children with absence seizures has not been published. We studied a population-based group of children with absence epilepsy to determine (a) how often absence seizures will be controlled after failure of the initial AED for lack of efficacy, and (b) whether failure of the initial AED predicts against long-term remission of absence epilepsy and for development of intractable epilepsy.

Assessment of clinical risk factors for drug-resistant epilepsy in children and teenagers

“…In our study, failure of the initial antiepileptic treatment turned out to be a comparably influential predictor of poor prognosis in epilepsy (Cramer's V = 0.65), which was also pointed out by Sillanpaa [6] and Wirrell et al [7].…”

“…The most frequently mentioned clinical factors include the following: initial antiepileptic treatment [6,7], considerable initial frequency of epileptic seizures [6,[8][9][10][11][12], occurrence of status epilepticus [6,[13][14][15][16][17], symptomatic aetiology of epilepsy [6,16,18], type of epilepsy/epileptic syndrome [11,13,14,16,[19][20][21][22], onset of epileptic seizures before the first birthday [13,15,18,23,24], abnormal results of neurological examination [8,18,23,24,25], and abnormalities detected in imaging [18,23] and EEG examinations [15,16,18].…”

Refractory absence seizures: An Italian multicenter retrospective study

“…Inversely, a favorable prognostic indicator is prompt seizure control after the introduction of an appropriate AED treatment. 14,15 In some cases, EEG abnormalities may persist into adulthood despite the subject being seizure free, such as a predisposition to hyperexcitability, but retrospective studies in adults may lack accurate initial data. Furthermore, children affected by CAE may have poor psychosocial adaptation.…”

Long-term prognosis for childhood and juvenile absence epilepsy

“…Recent studies discovered two gene mutations in CAE probands with further epileptic or other neurological features [19,27] and several susceptibility loci [8,12,13,14,20,24,26,27] supporting genetic heterogeneity and the hypothesis of fundamental biological differences within IGE syndromes and even CAE subsyndromes. These findings may account for the different prognostic scenarios for a child with CAE, namely either entering remission of absences or evolving into other IGE syndromes (e. g. JME) either with later development of GTCS or myoclonic seizures or both [8,13,28,29].…”