Epilepsy is a disease whose diagnosis and treatment are continuously undergoing development. Currently, epileptic symptoms can be controlled in 70% to 80% of affected patients with the administration of various antiepileptic drugs (AEDs) [1]. The rate of symptom recurrence is being increasingly diminished by the advancement of AEDs and drugs that can measure serum concentration [2]. However, AEDs are associated with poor drug compliance due to their numerous adverse effects and the need to consume them daily. These drawbacks are of particular concern for school-age children, in whom AEDs cause drowsiness, fatigue, and attention deficits that may impair their language and cognitive development [3].

Prior research has investigated whether the timing of discontinuing AED administration to pediatric patients can be calibrated so as to diminish the probability of seizure recurrence and, hence, the need to resume AED therapy [4]. For instance, Strozzi et al. [5] reported a seizure-free period of to 2 years to be suggestible for AED discontinuation. However, as only a few studies have considered the discontinuation of AEDs and the risk factors associated with seizure recurrence in children, the timing of AED discontinuation in pediatric patients remains controversial.

In this study, we sought to identify the recurrence rates of epilepsy after discontinuation of AEDs in pediatric patients. We also identified the risk factors associated with the recurrence of epilepsy.

The present study observed the overall recurrence rate within 1 year after the discontinuation of AEDs to be 19.7% (87/441). When evaluated according to the timing of AED discontinuation, the highest rate of recurrence was observed during AED tapering 43.7% (38/87). We further identified the following factors as being significantly associated with recurrence of epilepsy: the age at which AEDs were first administered and seizures were controlled, a history of epilepsy recurrence after previous discontinuations of AEDs, an episode of seizure during AED administration, and no improvement in EEG findings across AED administration.

When timing the discontinuation of AEDs, medical factors as well as other individual factors should be considered [6]. The will of patients and their caregiver, their economic conditions, the adverse effects of drugs, and comorbidity can also affect the decision to discontinue AED administration. Numerous studies have sought to elucidate the factors associated with the recurrence of epilepsy after the discontinuation of AEDs to help inform this decision. For instance, upon reviewing the results from various studies, the American Academy of Neurology reported in 1996 that seizure-free period of 2 to 5 years, normal results from neurological examination, and the normalization of EEG during treatment lessened the risk of recurrence [7]. In addition, the risk of recurrence reportedly increases when the cause of epilepsy is symptomatic [8-10] and decreases when patients show an early response to the first administration of AED [8,11].

Regarding the differences in the risk of recurrence according to the age at seizure onset, several reports have found that the risk increases in adolescence; Shinnar et al. [12] defined this period as beginning at the age of 12, while Dooley et al. [13] and Chung et al. [14] considered adolescence to begin at the age of 10. Emerson et al. [15] reported that the recurrence rate is higher when the patient experiences his or her first seizure at the age of 2 years or younger. Although recurrence rates according to the age at seizure onset were higher in the infancy and adolescence relative to those in early and late childhood, the differences were not statistically significant in this study.

In some studies, there was no association between recurrence and histories of recurrence after previous discontinuations of AEDs and when epilepsy recurred after previous discontinuations of AED, the re-administration of AEDs lead to the remission of epilepsy [13,16]. However, in our study, the rate of recurrence was 48.8% among the patients with histories of epilepsy recurrence after previous discontinuations of AED, while a rate of 16.7% was observed among the patients without epilepsy recurrence after previous discontinuations of AED.

As for episodes of seizure during administering AEDs, Chung et al. [14] reported the recurrence of seizures during administering AEDs did not appear to be related to relapse. However, Specchio and Beghi [11] reported a connection as in this study.

This study performed an analysis of EEG results obtained at the time of diagnosis and before the discontinuation of AEDs. While Shinnar et al. [12] and Emerson et al. [15] reported that EEG abnormalities identified before discontinuations of AED treatment cannot predict the risk of recurrence, we found that there was a significantly higher recurrence rate among patients whose EEG results did not improve than among those whose results did (43.1%, 14.5%, respectively). Hence, our study observed that improvement in EEG findings (across treatment) is more predictive of recurrence than is the EEG obtained at the time of diagnosis.

Hippocampal atrophy or sclerosis identified with MRI is reportedly associated with a high rate of epileptic recurrence [2]. On the other hand, Lossius et al. [17] reported that abnormal findings from MRI are not predictive factors for epilepsy recurrence. Similarly, our study found the recurrence rate to be 21.5% in the presence of radiographic abnormalities and 22.8% in their absence, but it was not a significant predictor of epileptic recurrence. That’s because the abnormal MRI was considered as a case of simple ventriculomegaly as well as lesions with a high recurrence rate such as hippocampal sclerosis.

According to some studies [6,11,18], neurological disability increase the risk of epilepsy recurrence. While the present study found that the recurrence rate of epilepsy was higher among patients with neurological disability than among those without them (25.9%, 17.6%, respectively), this difference was nonsignificant.

As for the number of AEDs administered to control seizures, some studies [14,15] have reported an increase in the recurrence rate if multiple anticonvulsants were administered, but in other study [12], the risk of recurrence did not increase even if multiple AEDs were administered likes our study..

There are some limitations in our study. It is limited by its retrospective nature as well as by its use of data obtained from a single institute. It was further limited by only having monitored the patients’ treatment when the patients revisited our hospital through the outpatient clinic or emergency room. Prospective studies that perform more regular monitoring of the patients’ clinical progress and an accurate analysis of treatment compliance are warranted. As the follow-up period for pediatric patients tends to be limited—unlike that for adult patients—and such patients generally visit a different department when they become adults, collaboration with the Department of Neurology will be needed in the future to analyze the long-term recurrence rates of epilepsy. Moreover, differences in the diagnosis rate caused by the development of EEG and radiographic equipment during the 10 years of follow-up period, as well as differences in the treatment rate caused by changes in therapeutic agents, could have biased our study results.

Finally, there are a few epilepsy syndromes that have a high probability of recurrence so that AEDs discontinuation is not suggested. These include Lennox-Gastaut syndrome, Dravet syndrome or severe brain lesions such as brain cell migration disorder [19]. However, we attempted to taper AEDs in our study if there was a clear improvement in EEG or when the caregiver requested an end to treatment for their children whose epilepsy had been well-controlled for at least 2 years without the improvement of EEG.

However, compared to some studies that have analyzed the factors affecting the recurrence of epilepsy in Korea [2,20], our study included a relatively large number of pediatric patients and that is the strength of this study.

In conclusion, the risk of recurrence may be high if (1) the patient was an infant or an adolescent when AEDs were first administered or when the seizures were controlled; (2) no (or less) improvement in EEG finding during AED administration; (3) he/she experienced seizure during AED administration; or (4) he/she has a history of epilepsy recurrence after previous discontinuation of AEDs. Therefore, the discontinuation of AEDs should be considered with greater care for these patients especially during tapering period.